SYNE1 p.Thr7356Thr

Variant names:

• chr6-152218380-G-A
• rs35686213
• NM_182961.4:c.22068C>T
• SYNE1 p.Thr7356Thr

Your query was ambiguous. Multiple possible variants found:

• chr6-152218380-G-A
• chr6-152218380-G-C
• chr6-152218380-G-T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-1 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -1 classification points (ACGS-UK Somatic Oncogenicity v2025). B4_Supporting

The NM_182961.4(SYNE1):c.22068C>T (p.Thr7356Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The gene SYNE1 is a known oncogene (CancerMine: 1 oncogene, 1 driver citations). The gene SYNE1 is a cancer driver gene (CancerMine: 1 oncogene, 1 driver citations). The variant allele was found at a cumulative frequency of 0.00153 (AC=2,470) in the gnomAD database across 1,613,228 control chromosomes, including 5 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0018. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Benign/Likely Benign (no review stars). The variant has been observed in cBioPortal in 2 samples across 2 studies and 1 cancer type; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (4 hom.)
• Consequence: SYNE1 NM_182961.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:7
• Conservation: PhyloP100: -0.475
• Publications: 3 publications found

Genes affected

SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SYNE1 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics, Orphanet
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant outside canonical splice sites (B4 supporting); Synonymous variant — splicing impact not confirmed absent; B4 supporting [-1]

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SYNE1 NM_182961.4	MANE Select	c.22068C>T p.Thr7356Thr	synonymous	Exon 121 of 146	Prot: NP_892006.3 UniProt:
	SYNE1 NM_033071.5		c.21855C>T p.Thr7285Thr	synonymous	Exon 120 of 146	Prot: NP_149062.2 UniProt:

SYNE1 NM_182961.4

MANE Select

HGVSc / HGVSpc.22068C>Tp.Thr7356Thr

Exon rankExon 121 of 146

synonymous

Prot: NP_892006.3UniProt: Q8NF91-1

SYNE1 NM_033071.5

HGVSc / HGVSpc.21855C>Tp.Thr7285Thr

Exon rankExon 120 of 146

synonymous

Prot: NP_149062.2UniProt: A0A0C4DG40Q8NF91-4

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SYNE1 ENST00000367255.10	TSL:1MANE Select	c.22068C>T p.Thr7356Thr	synonymous	Exon 121 of 146	Prot: ENSP00000356224.5 UniProt:
	SYNE1 ENST00000423061.6	TSL:1	c.21855C>T p.Thr7285Thr	synonymous	Exon 120 of 146	Prot: ENSP00000396024.1 UniProt:
	SYNE1 ENST00000367251.7	TSL:1	c.834C>T p.Thr278Thr	synonymous	Exon 6 of 31	Prot: ENSP00000356220.3 UniProt:

SYNE1 ENST00000367255.10

TSL:1MANE Select

HGVSc / HGVSpc.22068C>Tp.Thr7356Thr

Exon rankExon 121 of 146

synonymous

Prot: ENSP00000356224.5UniProt: Q8NF91-1

SYNE1 ENST00000423061.6

TSL:1

HGVSc / HGVSpc.21855C>Tp.Thr7285Thr

Exon rankExon 120 of 146

synonymous

Prot: ENSP00000396024.1UniProt: A0A0C4DG40

SYNE1 ENST00000367251.7

TSL:1

HGVSc / HGVSpc.834C>Tp.Thr278Thr

Exon rankExon 6 of 31

synonymous

Prot: ENSP00000356220.3UniProt: H0Y325

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00107	AC:162	Hom:1	AN:151328	Cov:31
GnomAD2 exomes	AF: 0.000971	AC:244	Hom:	AN:251248	Cov:
GnomAD4 exome	AF: 0.00158	AC:2308	Hom:4	AN:1461786	Cov:35
GnomAD4 genome	AF: 0.00107	AC:162	Hom:1	AN:151442	Cov:31
TOPMed (Bravo)	AF: 0.00119	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00108	AC:106	Hom:0	AN:98078	Cov:
Local & regional cohorts 7 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.000427	AC:1	Hom:0	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0000492	AC:	Hom:	AN:	Cov:
ESP6500 (Exome Variant Server)	AF: 0.00154	AC:20	Hom:	AN:13006	Cov:
Korea4K (4,157 Koreans)	AF: 0.00359	AC:26	Hom:	AN:7234	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.00193	AC:237	Hom:2	AN:122528	Cov:
Turkish Variome	AF: 0.000298	AC:2	Hom:0	AN:6716	Cov:
UK10K	AF: 0.00159	AC:12	Hom:	AN:7562	Cov:

Showing 13 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.000900 *	10	11112	0.00136 *	24	17612
BipEx(Bipolar disorder (including schizoaffective))	0.00144	41	28420	0.00156	45	28844
Epi25(Epilepsy)	0.00112	47	41956	0.00139	93	66878
SCHEMA(Schizophrenia)	0.00112	129	114676	0.00112	196	175350

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	-	2	not specified (2)
-	1	-	Autosomal recessive ataxia, Beauce type (1)
-	-	1	Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)
-	-	1	Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	13
BayesDel_noAF	Benign	-0.35
CADD	Benign	5.0
DANN	Benign	0.63
GPN-Star LLR	N/A	-2.0
GPN-Star score	N/A	2.0
Mutation Taster	N/A	97/3	polymorphism
PhyloP100	Benign	-0.47
PromoterAI	N/A	-0.033	Neutral

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.040

Showing 1 of 1 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs35686213;

hg19: chr6-152539515;

COSMIC: COSV99556987;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar