rs9953514

Positions:

• chr18-7831267-G-A
• chr18-7831267-G-C

Variant summary

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

The NM_001105244.2(PTPRM):​c.197-56839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,018 control chromosomes in the GnomAD database, including 165 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 0.027 (165 hom., cov: 32)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRM	NM_001105244.2	c.197-56839G>A		intron_variant		ENST00000580170.6	NP_001098714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6	c.197-56839G>A		intron_variant		1	NM_001105244.2	ENSP00000463325.1
PTPRM	ENST00000332175.12	c.197-56839G>A		intron_variant		1		ENSP00000331418.8
PTPRM	ENST00000400053.8	c.11-56839G>A		intron_variant		5		ENSP00000382927.4
PTPRM	ENST00000400060.8	c.-3362-56839G>A		intron_variant		5		ENSP00000382933.5

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4079 AN: 151898 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0268 AC: 4081 AN: 152018 Hom.: 165 Cov.: 32 AF XY: 0.0252 AC XY: 1869 AN XY: 74304

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.00781 Hom.: 9

Bravo AF: 0.0315

Asia WGS AF: 0.00434 AC: 15 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.014
DANN	Benign	0.39

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: rs9953514; hg19: chr18-7831265;