chr14-95490235-G-C

Position:

• chr14-95490235-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.-14-14400C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,196 control chromosomes in the GnomAD database, including 31,290 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 0.63 (31290 hom., cov: 34)
• Consequence: SYNE3 NM_152592.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE3	NM_152592.6	c.-14-14400C>G		intron_variant		ENST00000682763.1	NP_689805.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE3	ENST00000682763.1	c.-14-14400C>G		intron_variant			NM_152592.6	ENSP00000507501	P4

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96336 AN: 152078 Hom.: 31247 Cov.: 34

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.634 AC: 96435 AN: 152196 Hom.: 31290 Cov.: 34 AF XY: 0.636 AC XY: 47322 AN XY: 74422

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.648

Alfa AF: 0.596 Hom.: 3460

Bravo AF: 0.643

Asia WGS AF: 0.662 AC: 2304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs734313; hg19: chr14-95956572;