rs2024863

Variant names:

• chr14-95457333-A-C
• rs2024863
• NM_152592.6:c.633T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-95457333-A-C
• chr14-95457333-A-G
• chr14-95457333-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152592.6(SYNE3):​c.633T>G​(p.Arg211Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,613,212 control chromosomes in the GnomAD database, including 234,972 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (28082 hom., cov: 31)
  • Exomes 𝑓: 0.53 (206890 hom.)
• Consequence: SYNE3 NM_152592.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 17 publications found

Genes affected

SYNE3 (HGNC:19861): (spectrin repeat containing nuclear envelope family member 3) Enables actin filament binding activity and cytoskeleton-nuclear membrane anchor activity. Involved in cytoskeleton organization; establishment of protein localization to membrane; and regulation of cell shape. Located in nuclear membrane. Part of meiotic nuclear membrane microtubule tethering complex. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.667 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152592.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	NM_152592.6	MANE Select	c.633T>G	p.Arg211Arg	synonymous	Exon 5 of 18	NP_689805.3
	SYNE3	NM_001363692.2		c.633T>G	p.Arg211Arg	synonymous	Exon 5 of 18	NP_001350621.1	Q6ZMZ3-2
	SYNE3	NM_001384281.1		c.633T>G	p.Arg211Arg	synonymous	Exon 5 of 10	NP_001371210.1	Q6ZMZ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	ENST00000682763.1	MANE Select	c.633T>G	p.Arg211Arg	synonymous	Exon 5 of 18	ENSP00000507501.1	Q6ZMZ3-1
	SYNE3	ENST00000334258.9	TSL:1	c.633T>G	p.Arg211Arg	synonymous	Exon 4 of 17	ENSP00000334308.4	Q6ZMZ3-1
	SYNE3	ENST00000553340.1	TSL:1	c.633T>G	p.Arg211Arg	synonymous	Exon 4 of 9	ENSP00000450774.1	Q6ZMZ3-3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91127 AN: 151718 Hom.: 28046 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.585

GnomAD2 exomes AF: 0.578 AC: 144842 AN: 250612 AF XY: 0.564

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.765

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.614

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.528 AC: 771971 AN: 1461376 Hom.: 206890 Cov.: 56 AF XY: 0.528 AC XY: 383505 AN XY: 726978

African (AFR) AF: 0.753 AC: 25220 AN: 33476

American (AMR) AF: 0.753 AC: 33676 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 13943 AN: 26114

East Asian (EAS) AF: 0.551 AC: 21877 AN: 39696

South Asian (SAS) AF: 0.538 AC: 46346 AN: 86202

European-Finnish (FIN) AF: 0.528 AC: 28129 AN: 53272

Middle Eastern (MID) AF: 0.553 AC: 3189 AN: 5766

European-Non Finnish (NFE) AF: 0.510 AC: 567162 AN: 1111768

Other (OTH) AF: 0.537 AC: 32429 AN: 60378

GnomAD4 genome AF: 0.601 AC: 91219 AN: 151836 Hom.: 28082 Cov.: 31 AF XY: 0.602 AC XY: 44681 AN XY: 74172

African (AFR) AF: 0.738 AC: 30576 AN: 41412

American (AMR) AF: 0.683 AC: 10409 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3472

East Asian (EAS) AF: 0.603 AC: 3098 AN: 5136

South Asian (SAS) AF: 0.538 AC: 2583 AN: 4804

European-Finnish (FIN) AF: 0.526 AC: 5529 AN: 10520

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35139 AN: 67930

Other (OTH) AF: 0.583 AC: 1229 AN: 2108

Alfa AF: 0.550 Hom.: 37509

Bravo AF: 0.621

Asia WGS AF: 0.573 AC: 1996 AN: 3478

EpiCase AF: 0.508

EpiControl AF: 0.517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.55
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2024863; hg19: chr14-95923670; COSMIC: COSV62079652; COSMIC: COSV62079652;