rs12640626

Positions:

• chr4-175705121-G-A
• chr4-175705121-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.38-3354C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,126 control chromosomes in the GnomAD database, including 20,476 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 0.49 (20476 hom., cov: 33)
• Consequence: GPM6A NM_201591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.13

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPM6A	NM_201591.3	c.38-3354C>T		intron_variant		ENST00000393658.7	NP_963885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPM6A	ENST00000393658.7	c.38-3354C>T		intron_variant		1	NM_201591.3	ENSP00000377268	P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74086 AN: 152008 Hom.: 20469 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.487 AC: 74116 AN: 152126 Hom.: 20476 Cov.: 33 AF XY: 0.494 AC XY: 36730 AN XY: 74352

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.521

Alfa AF: 0.564 Hom.: 24507

Bravo AF: 0.481

Asia WGS AF: 0.654 AC: 2272 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	0.028
DANN	Benign	0.69

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: rs12640626; hg19: chr4-176626272;