rs17599018

Variant names:

• chr4-175740936-T-C
• rs17599018
• NM_201591.3:c.38-39169A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201591.3(GPM6A):​c.38-39169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,998 control chromosomes in the GnomAD database, including 2,044 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 0.15 (2044 hom., cov: 32)
• Consequence: GPM6A NM_201591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6A	NM_201591.3	c.38-39169A>G		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.38-39169A>G		intron_variant	Intron 1 of 6	1	NM_201591.3	ENSP00000377268.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23175 AN: 151880 Hom.: 2045 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.152 AC: 23175 AN: 151998 Hom.: 2044 Cov.: 32 AF XY: 0.152 AC XY: 11307 AN XY: 74264

African (AFR) AF: 0.110 AC: 4583 AN: 41544

American (AMR) AF: 0.116 AC: 1778 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3468

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.0306 AC: 148 AN: 4830

European-Finnish (FIN) AF: 0.252 AC: 2657 AN: 10558

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13091 AN: 67846

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.171 Hom.: 5163

Bravo AF: 0.142

Asia WGS AF: 0.0290 AC: 103 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	2.1
DANN	Benign	0.56
PhyloP100		0.038
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: rs17599018; hg19: chr4-176662087;