rs11622887

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE3	NM_152592.6	c.-14-275T>G		intron_variant	Intron 1 of 17	ENST00000682763.1	NP_689805.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE3	ENST00000682763.1	c.-14-275T>G		intron_variant	Intron 1 of 17		NM_152592.6	ENSP00000507501.1

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

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.487

Alfa AF: 0.511 Hom.: 11046

Bravo AF: 0.510

Asia WGS AF: 0.554 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

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