chr14-88550324-T-G

Position:

• chr14-88550324-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007039.4(PTPN21):​c.94A>C​(p.Asn32His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PTPN21 NM_007039.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.12

Genes affected

PTPN21 (HGNC:9651): (protein tyrosine phosphatase non-receptor type 21) 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 contains an N-terminal domain, similar to cytoskeletal- associated proteins including band 4.1, ezrin, merlin, and radixin. This PTP was shown to specially interact with BMX/ETK, a member of Tec tyrosine kinase family characterized by a multimodular structures including PH, SH3, and SH2 domains. The interaction of this PTP with BMX kinase was found to increase the activation of STAT3, but not STAT2 kinase. Studies of the similar gene in mice suggested the possible roles of this PTP in liver regeneration and spermatogenesis. [provided by RefSeq, Jul 2008]

PTPN21 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36568037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.94A>C	p.Asn32His	missense_variant	2/19	ENST00000556564.6	NP_008970.2
PTPN21	XM_005267287.4	c.94A>C	p.Asn32His	missense_variant	2/19		XP_005267344.1
PTPN21	XM_011536367.4	c.94A>C	p.Asn32His	missense_variant	2/19		XP_011534669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.94A>C	p.Asn32His	missense_variant	2/19	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;.;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.3	N;N;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0080	D;D;T
Sift4G	Uncertain	0.012	D;D;.
Polyphen		0.90	P;P;B
Vest4		0.43
MutPred		0.54		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.80
MPC		0.74
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.088

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: rs193920899; hg19: chr14-89016668; COSMIC: COSV60850160; COSMIC: COSV60850160;