chr4-175705121-G-A

Variant names:

• chr4-175705121-G-A
• rs12640626
• NM_201591.3:c.38-3354C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPM6A	NM_201591.3	c.38-3354C>T		intron_variant	Intron 1 of 6	ENST00000393658.7	NP_963885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6A	ENST00000393658.7	c.38-3354C>T		intron_variant	Intron 1 of 6	1	NM_201591.3	ENSP00000377268.2

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

African (AFR) AF: 0.210 AC: 8725 AN: 41500

American (AMR) AF: 0.628 AC: 9603 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2196 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3774 AN: 5178

South Asian (SAS) AF: 0.616 AC: 2963 AN: 4812

European-Finnish (FIN) AF: 0.553 AC: 5849 AN: 10574

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39168 AN: 67992

Other (OTH) AF: 0.521 AC: 1100 AN: 2112

Alfa AF: 0.553 Hom.: 35247

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
PhyloP100		-5.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12640626; hg19: chr4-176626272;