14-95477211-T-C

Variant names:

• chr14-95477211-T-C
• rs8020368
• NM_152592.6:c.-14-1376A>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.-14-1376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,104 control chromosomes in the GnomAD database, including 23,978 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 0.56 (23978 hom., cov: 32)
• Consequence: SYNE3 NM_152592.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE3	NM_152592.6	c.-14-1376A>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.-14-1376A>G		intron_variant	Intron 1 of 17		NM_152592.6	ENSP00000507501.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84516 AN: 151986 Hom.: 23943 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.556 AC: 84601 AN: 152104 Hom.: 23978 Cov.: 32 AF XY: 0.558 AC XY: 41499 AN XY: 74352

African (AFR) AF: 0.672 AC: 27908 AN: 41504

American (AMR) AF: 0.530 AC: 8098 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3468

East Asian (EAS) AF: 0.500 AC: 2580 AN: 5164

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4824

European-Finnish (FIN) AF: 0.536 AC: 5656 AN: 10558

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33954 AN: 67980

Other (OTH) AF: 0.520 AC: 1098 AN: 2110

Alfa AF: 0.529 Hom.: 33395

Bravo AF: 0.555

Asia WGS AF: 0.580 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.082
DANN	Benign	0.41
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs8020368; hg19: chr14-95943548;