18-7717567-A-T

Variant names:

• chr18-7717567-A-T
• rs582683
• NM_001105244.2:c.74-56582A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105244.2(PTPRM):​c.74-56582A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,156 control chromosomes in the GnomAD database, including 40,205 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 0.71 (40205 hom., cov: 33)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

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.74-56582A>T		intron	N/A	NP_001098714.1	P28827-2
	PTPRM	NM_002845.4		c.74-56582A>T		intron	N/A	NP_002836.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	ENST00000580170.6	TSL:1 MANE Select	c.74-56582A>T		intron	N/A	ENSP00000463325.1	P28827-2
	PTPRM	ENST00000332175.12	TSL:1	c.74-56582A>T		intron	N/A	ENSP00000331418.8	P28827-1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107729 AN: 152038 Hom.: 40132 Cov.: 33

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.709 AC: 107870 AN: 152156 Hom.: 40205 Cov.: 33 AF XY: 0.710 AC XY: 52797 AN XY: 74366

African (AFR) AF: 0.915 AC: 38012 AN: 41540

American (AMR) AF: 0.694 AC: 10612 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2226 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5142 AN: 5158

South Asian (SAS) AF: 0.864 AC: 4172 AN: 4828

European-Finnish (FIN) AF: 0.486 AC: 5133 AN: 10570

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40339 AN: 67986

Other (OTH) AF: 0.692 AC: 1464 AN: 2116

Alfa AF: 0.629 Hom.: 3651

Bravo AF: 0.730

Asia WGS AF: 0.924 AC: 3212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs582683; hg19: chr18-7717565;