NM_152592.6:c.-14-275T>G

Variant names:

• chr14-95476110-A-C
• rs11622887
• NM_152592.6:c.-14-275T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152592.6(SYNE3):​c.-14-275T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,142 control chromosomes in the GnomAD database, including 21,096 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 0.52 (21096 hom., cov: 34)
• Consequence: SYNE3 NM_152592.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 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.-14-275T>G		intron	N/A	NP_689805.3
	SYNE3	NM_001363692.2		c.-14-275T>G		intron	N/A	NP_001350621.1	Q6ZMZ3-2
	SYNE3	NM_001384281.1		c.-14-275T>G		intron	N/A	NP_001371210.1	Q6ZMZ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	ENST00000682763.1	MANE Select	c.-14-275T>G		intron	N/A	ENSP00000507501.1	Q6ZMZ3-1
	SYNE3	ENST00000965390.1		c.-14-275T>G		intron	N/A	ENSP00000635449.1
	SYNE3	ENST00000965385.1		c.-14-275T>G		intron	N/A	ENSP00000635444.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79362 AN: 152024 Hom.: 21070 Cov.: 34

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.486

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79437 AN: 152142 Hom.: 21096 Cov.: 34 AF XY: 0.521 AC XY: 38777 AN XY: 74370

African (AFR) AF: 0.610 AC: 25306 AN: 41504

American (AMR) AF: 0.388 AC: 5938 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1552 AN: 3468

East Asian (EAS) AF: 0.491 AC: 2535 AN: 5162

South Asian (SAS) AF: 0.604 AC: 2914 AN: 4822

European-Finnish (FIN) AF: 0.532 AC: 5627 AN: 10576

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33885 AN: 67994

Other (OTH) AF: 0.487 AC: 1029 AN: 2114

Alfa AF: 0.519 Hom.: 17625

Bravo AF: 0.510

Asia WGS AF: 0.554 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.39
PhyloP100		-0.40
PromoterAI		0.058	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11622887; hg19: chr14-95942447; COSMIC: COSV62083032;