chr18-8332976-G-A

Variant names:

• chr18-8332976-G-A
• rs582420
• NM_001105244.2:c.2957-10447G>A

Variant summary

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

The NM_001105244.2(PTPRM):​c.2957-10447G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,996 control chromosomes in the GnomAD database, including 5,910 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 0.27 (5910 hom., cov: 33)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 2 publications found

Genes affected

PTPRM (HGNC:9675): (protein tyrosine phosphatase receptor type M) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRM	NM_001105244.2	c.2957-10447G>A		intron_variant	Intron 22 of 32	ENST00000580170.6	NP_001098714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6	c.2957-10447G>A		intron_variant	Intron 22 of 32	1	NM_001105244.2	ENSP00000463325.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41346 AN: 151878 Hom.: 5907 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.272 AC: 41382 AN: 151996 Hom.: 5910 Cov.: 33 AF XY: 0.265 AC XY: 19682 AN XY: 74294

African (AFR) AF: 0.329 AC: 13637 AN: 41456

American (AMR) AF: 0.219 AC: 3347 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3468

East Asian (EAS) AF: 0.0595 AC: 308 AN: 5174

South Asian (SAS) AF: 0.177 AC: 855 AN: 4822

European-Finnish (FIN) AF: 0.272 AC: 2868 AN: 10544

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18782 AN: 67962

Other (OTH) AF: 0.277 AC: 584 AN: 2108

Alfa AF: 0.258 Hom.: 4331

Bravo AF: 0.273

Asia WGS AF: 0.135 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.61
PhyloP100		-0.14
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: rs582420; hg19: chr18-8332974;