rs12895389

Positions:

• chr14-95425937-G-A

Variant summary

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

The NM_152592.6(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 NM_152592.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE3	NM_152592.6	c.2727+6142C>T		intron_variant		ENST00000682763.1
SYNE3	NM_001363692.2	c.2712+6142C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE3	ENST00000682763.1	c.2727+6142C>T		intron_variant			NM_152592.6	P4
SYNE3	ENST00000334258.9	c.2727+6142C>T		intron_variant		1		P4
SYNE3	ENST00000554873.5	c.1998+6142C>T		intron_variant		5
SYNE3	ENST00000557275.5	c.2712+6142C>T		intron_variant		2		A1

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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0856

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.121

Alfa AF: 0.138 Hom.: 1532

Bravo AF: 0.121

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs12895389; hg19: chr14-95892274;