chr18-8013718-C-T

Position:

• chr18-8013718-C-T

Variant summary

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

The NM_001105244.2(PTPRM):​c.1133-55968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,018 control chromosomes in the GnomAD database, including 4,706 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 0.24 (4706 hom., cov: 32)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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]

ENSG00000286627 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRM	NM_001105244.2	c.1133-55968C>T		intron_variant		ENST00000580170.6	NP_001098714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6	c.1133-55968C>T		intron_variant		1	NM_001105244.2	ENSP00000463325.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36520 AN: 151900 Hom.: 4693 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.240 AC: 36560 AN: 152018 Hom.: 4706 Cov.: 32 AF XY: 0.237 AC XY: 17576 AN XY: 74316

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.258

Alfa AF: 0.218 Hom.: 7727

Bravo AF: 0.250

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.36

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: rs6506544; hg19: chr18-8013716;