19-3783867-G-T

Position:

• chr19-3783867-G-T

Variant summary

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

The NM_139355.3(MATK):​c.529C>A​(p.His177Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATK NM_139355.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

Genes affected

MATK (HGNC:6906): (megakaryocyte-associated tyrosine kinase) The protein encoded by this gene has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer. Three alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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=0.27234322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATK	NM_139355.3	c.529C>A	p.His177Asn	missense_variant	6/14	ENST00000310132.11	NP_647612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATK	ENST00000310132.11	c.529C>A	p.His177Asn	missense_variant	6/14	1	NM_139355.3	ENSP00000308734.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.532C>A (p.H178N) alteration is located in exon 6 (coding exon 5) of the MATK gene. This alteration results from a C to A substitution at nucleotide position 532, causing the histidine (H) at amino acid position 178 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.22	.;.;T;T;.;T;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D;D;D;D;.;D;D;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.65	.;.;N;.;.;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.19	.;N;N;.;N;.;.;.
REVEL	Benign	0.28
Sift	Benign	0.079	.;T;T;.;T;.;.;.
Sift4G	Benign	0.33	T;T;T;T;T;D;T;.
Polyphen		0.36	.;.;B;.;.;.;.;.
Vest4		0.41
MutPred		0.45		.;.;Loss of stability (P = 0.105);Loss of stability (P = 0.105);.;.;.;.;
MVP		0.88
MPC		0.64
ClinPred		0.28	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.57

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: chr19-3783865;