18-7774192-T-G

Variant names:

• chr18-7774192-T-G
• NM_001105244.2:c.117T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001105244.2(PTPRM):​c.117T>G​(p.Ser39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTPRM NM_001105244.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRM	NM_001105244.2	c.117T>G	p.Ser39Arg	missense_variant	Exon 2 of 33	ENST00000580170.6	NP_001098714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6	c.117T>G	p.Ser39Arg	missense_variant	Exon 2 of 33	1	NM_001105244.2	ENSP00000463325.1
PTPRM	ENST00000332175.12	c.117T>G	p.Ser39Arg	missense_variant	Exon 2 of 31	1		ENSP00000331418.8
PTPRM	ENST00000400053	c.-70T>G		5_prime_UTR_variant	Exon 2 of 31	5		ENSP00000382927.4
PTPRM	ENST00000400060	c.-3442T>G		5_prime_UTR_variant	Exon 1 of 32	5		ENSP00000382933.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460534 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726710

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.18
Sift	Benign	0.18	.;T
Sift4G	Benign	0.17	T;T
Polyphen		1.0	.;D
Vest4		0.64
MutPred		0.28		Gain of catalytic residue at S39 (P = 0.0576);Gain of catalytic residue at S39 (P = 0.0576);
MVP		0.75
MPC		1.1
ClinPred		0.90	D
GERP RS		1.6
Varity_R		0.64
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-7774190;