rs727917

chr4-175646208-G-Achr4-175646208-G-C

Variant summary

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

The NM_201591.3(GPM6A):c.542-5379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,986 control chromosomes in the GnomAD database, including 40,748 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 0.71 (40748 hom., cov: 32)
• Consequence: GPM6A NM_201591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735

Genes affected

GPM6A (HGNC:4460): (glycoprotein M6A) Predicted to enable calcium channel activity. Involved in neuron migration and stem cell differentiation. Located in extracellular exosome. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPM6A	NM_201591.3	c.542-5379C>T		intron_variant		ENST00000393658.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6A	ENST00000393658.7	c.542-5379C>T		intron_variant		1	NM_201591.3	P1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107465 AN: 151868 Hom.: 40746 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.707 AC: 107497 AN: 151986 Hom.: 40748 Cov.: 32 AF XY: 0.708 AC XY: 52612 AN XY: 74322

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.747

Alfa AF: 0.770 Hom.: 5888

Bravo AF: 0.692

Asia WGS AF: 0.766 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.1
Dann	Benign	0.43

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: rs727917; hg19: chr4-176567359;