chr18-7813241-T-C

Position:

• chr18-7813241-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105244.2(PTPRM):​c.196+38970T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,144 control chromosomes in the GnomAD database, including 36,023 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 0.68 (36023 hom., cov: 33)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRM	NM_001105244.2	c.196+38970T>C		intron_variant		ENST00000580170.6	NP_001098714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6	c.196+38970T>C		intron_variant		1	NM_001105244.2	ENSP00000463325	A1
PTPRM	ENST00000332175.12	c.196+38970T>C		intron_variant		1		ENSP00000331418	P4
PTPRM	ENST00000400053.8	c.10+38970T>C		intron_variant		5		ENSP00000382927
PTPRM	ENST00000400060.8	c.-3363+38970T>C		intron_variant		5		ENSP00000382933

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102868 AN: 152026 Hom.: 35970 Cov.: 33

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.677 AC: 102984 AN: 152144 Hom.: 36023 Cov.: 33 AF XY: 0.681 AC XY: 50642 AN XY: 74364

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.661

Alfa AF: 0.609 Hom.: 13684

Bravo AF: 0.696

Asia WGS AF: 0.855 AC: 2974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.84
DANN	Benign	0.42

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: rs364418; hg19: chr18-7813239;