chr18-7584296-G-A

Variant names:

• chr18-7584296-G-A
• rs4798571
• NM_001105244.2:c.73+16405G>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.73+16405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,034 control chromosomes in the GnomAD database, including 17,702 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 0.39 (17702 hom., cov: 32)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRM	NM_001105244.2	c.73+16405G>A		intron_variant	Intron 1 of 32	ENST00000580170.6	NP_001098714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6	c.73+16405G>A		intron_variant	Intron 1 of 32	1	NM_001105244.2	ENSP00000463325.1
PTPRM	ENST00000332175.12	c.73+16405G>A		intron_variant	Intron 1 of 30	1		ENSP00000331418.8

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58732 AN: 151916 Hom.: 17629 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.387 AC: 58874 AN: 152034 Hom.: 17702 Cov.: 32 AF XY: 0.389 AC XY: 28945 AN XY: 74330

African (AFR) AF: 0.803 AC: 33320 AN: 41480

American (AMR) AF: 0.387 AC: 5897 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3701 AN: 5156

South Asian (SAS) AF: 0.452 AC: 2176 AN: 4818

European-Finnish (FIN) AF: 0.107 AC: 1135 AN: 10574

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10815 AN: 67968

Other (OTH) AF: 0.357 AC: 755 AN: 2114

Alfa AF: 0.304 Hom.: 2007

Bravo AF: 0.425

Asia WGS AF: 0.608 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.37
PhyloP100		0.12
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: rs4798571; hg19: chr18-7584294;