14-95496476-G-C

Position:

• chr14-95496476-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152592.6(SYNE3):​c.-15+20120C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,070 control chromosomes in the GnomAD database, including 31,859 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 0.64 (31859 hom., cov: 32)
• Consequence: SYNE3 NM_152592.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE3	NM_152592.6	c.-15+20120C>G		intron_variant		ENST00000682763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE3	ENST00000682763.1	c.-15+20120C>G		intron_variant			NM_152592.6	P4

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97605 AN: 151952 Hom.: 31825 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.642 AC: 97697 AN: 152070 Hom.: 31859 Cov.: 32 AF XY: 0.645 AC XY: 47911 AN XY: 74324

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.653

Alfa AF: 0.605 Hom.: 3361

Bravo AF: 0.650

Asia WGS AF: 0.658 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.36
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1885423; hg19: chr14-95962813;