rs12895389

Variant names:

• chr14-95425937-G-A
• rs12895389
• NM_152592.6:c.2727+6142C>T

Variant summary

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

The ENST00000682763.1(SYNE3):​c.2727+6142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,272 control chromosomes in the GnomAD database, including 1,237 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 0.12 (1237 hom., cov: 33)
• Consequence: SYNE3 ENST00000682763.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682763.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	NM_152592.6	MANE Select	c.2727+6142C>T		intron	N/A	NP_689805.3
	SYNE3	NM_001363692.2		c.2712+6142C>T		intron	N/A	NP_001350621.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	ENST00000682763.1	MANE Select	c.2727+6142C>T		intron	N/A	ENSP00000507501.1
	SYNE3	ENST00000334258.9	TSL:1	c.2727+6142C>T		intron	N/A	ENSP00000334308.4
	SYNE3	ENST00000557275.5	TSL:2	c.2712+6142C>T		intron	N/A	ENSP00000450562.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18961 AN: 152154 Hom.: 1237 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.124 AC: 18955 AN: 152272 Hom.: 1237 Cov.: 33 AF XY: 0.121 AC XY: 8983 AN XY: 74458

African (AFR) AF: 0.107 AC: 4438 AN: 41556

American (AMR) AF: 0.0856 AC: 1310 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3470

East Asian (EAS) AF: 0.114 AC: 592 AN: 5184

South Asian (SAS) AF: 0.122 AC: 588 AN: 4826

European-Finnish (FIN) AF: 0.0991 AC: 1051 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10169 AN: 68012

Other (OTH) AF: 0.121 AC: 255 AN: 2110

Alfa AF: 0.133 Hom.: 2096

Bravo AF: 0.121

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.80
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12895389; hg19: chr14-95892274;