rs150672767

Variant names:

• chr1-198755930-G-A
• rs150672767
• NM_002838.5:c.3670G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-198755930-G-A
• chr1-198755930-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_002838.5(PTPRC):​c.3670G>A​(p.Val1224Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,611,676 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1224F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (9 hom.)
• Consequence: PTPRC NM_002838.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:6
• Conservation: PhyloP100: 0.0820
• Publications: 6 publications found

Genes affected

PTPRC (HGNC:9666): (protein tyrosine phosphatase receptor type C) 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, mitosis, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jun 2012]

MIR181A1HG (HGNC:48659): (MIR181A1 host gene)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004925579).
• BP6: Variant 1-198755930-G-A is Benign according to our data. Variant chr1-198755930-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 440224.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0015 (228/151960) while in subpopulation AMR AF = 0.00164 (25/15258). AF 95% confidence interval is 0.00114. There are 0 homozygotes in GnomAd4. There are 101 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002838.5. 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
	PTPRC	NM_002838.5	MANE Select	c.3670G>A	p.Val1224Ile	missense	Exon 33 of 33	NP_002829.3
	PTPRC	NM_080921.4		c.3187G>A	p.Val1063Ile	missense	Exon 30 of 30	NP_563578.2	P08575-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.3670G>A	p.Val1224Ile	missense	Exon 33 of 33	ENSP00000411355.3	P08575-3
	PTPRC	ENST00000348564.12	TSL:1	c.3187G>A	p.Val1063Ile	missense	Exon 30 of 30	ENSP00000306782.7	P08575-4
	PTPRC	ENST00000697631.1		c.3385G>A	p.Val1129Ile	missense	Exon 31 of 31	ENSP00000513363.1	P08575-8

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 228 AN: 151842 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00194 AC: 485 AN: 250252 AF XY: 0.00208

Gnomad AFR exome AF: 0.000925

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00159

Gnomad OTH exome AF: 0.00460

GnomAD4 exome AF: 0.00149 AC: 2176 AN: 1459716 Hom.: 9 Cov.: 31 AF XY: 0.00152 AC XY: 1106 AN XY: 726312

African (AFR) AF: 0.00132 AC: 44 AN: 33370

American (AMR) AF: 0.00175 AC: 78 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 540 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86178

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53398

Middle Eastern (MID) AF: 0.00556 AC: 32 AN: 5756

European-Non Finnish (NFE) AF: 0.00114 AC: 1261 AN: 1110390

Other (OTH) AF: 0.00335 AC: 202 AN: 60284

GnomAD4 genome AF: 0.00150 AC: 228 AN: 151960 Hom.: 0 Cov.: 32 AF XY: 0.00136 AC XY: 101 AN XY: 74256

African (AFR) AF: 0.00113 AC: 47 AN: 41478

American (AMR) AF: 0.00164 AC: 25 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 67944

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00206 Hom.: 4

Bravo AF: 0.00176

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00158 AC: 192

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00261

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	3	not provided (5)
-	-	1	Immunodeficiency 104 (1)
-	-	1	not specified (1)
-	-	1	PTPRC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.0030
DANN	Benign	0.26
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.82	T
PhyloP100		0.082
PrimateAI	Benign	0.25	T
REVEL	Uncertain	0.35
Sift4G	Benign	0.55	T
Vest4		0.097
MVP		0.25
MPC		0.14
ClinPred		0.0021	T
GERP RS		-6.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.11
Mutation Taster		=98/2	polymorphism

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: rs150672767; hg19: chr1-198725059; COSMIC: COSV99049535; COSMIC: COSV99049535;