rs752156618

Variant names:

• chr18-7774150-T-C
• rs752156618
• NM_001105244.2:c.75T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001105244.2(PTPRM):​c.75T>C​(p.Gly25Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,454,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: PTPRM NM_001105244.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0003146
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.746
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 18-7774150-T-C is Benign according to our data. Variant chr18-7774150-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3046402.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.746 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105244.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	NM_001105244.2	MANE Select	c.75T>C	p.Gly25Gly	splice_region synonymous	Exon 2 of 33	NP_001098714.1	P28827-2
	PTPRM	NM_002845.4		c.75T>C	p.Gly25Gly	splice_region synonymous	Exon 2 of 31	NP_002836.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	ENST00000580170.6	TSL:1 MANE Select	c.75T>C	p.Gly25Gly	splice_region synonymous	Exon 2 of 33	ENSP00000463325.1	P28827-2
	PTPRM	ENST00000332175.12	TSL:1	c.75T>C	p.Gly25Gly	splice_region synonymous	Exon 2 of 31	ENSP00000331418.8	P28827-1
	PTPRM	ENST00000400053.8	TSL:5	c.-112T>C		splice_region	Exon 2 of 31	ENSP00000382927.4	E7EPS8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249960 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1454406 Hom.: 0 Cov.: 31 AF XY: 0.00000691 AC XY: 5 AN XY: 723900

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105852

Other (OTH) AF: 0.00 AC: 0 AN: 60146

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTPRM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.75
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.034
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: rs752156618; hg19: chr18-7774148;