Variant 19-3778312-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_139355.3(MATK):c.1395C>T(p.Pro465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,576,168 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 41 hom. )

Consequence

MATK
NM_139355.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.02

Variant links:

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]

MATK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-3778312-G-A is Benign according to our data. Variant chr19-3778312-G-A is described in ClinVar as [Benign]. Clinvar id is 785911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00289 (440/152306) while in subpopulation AMR AF= 0.0261 (400/15304). AF 95% confidence interval is 0.024. There are 10 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATK	NM_139355.3 linkuse as main transcript	c.1395C>T	p.Pro465=	synonymous_variant	14/14	ENST00000310132.11	NP_647612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATK	ENST00000310132.11 linkuse as main transcript	c.1395C>T	p.Pro465=	synonymous_variant	14/14	1	NM_139355.3	ENSP00000308734		P42679-1

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

441

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00493

AC:

1061

AN:

215346

Hom.:

AF XY:

0.00394

AC XY:

467

AN XY:

118460

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.0396

Gnomad ASJ exome

AF:

0.000257

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000388

Gnomad FIN exome

AF:

0.000768

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00105

AC:

1489

AN:

1423862

Hom.:

Cov.:

AF XY:

0.000878

AC XY:

620

AN XY:

706412

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.0382

Gnomad4 ASJ exome

AF:

0.000165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.0000328

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152306

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.0261

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000715

Hom.:

Bravo

AF:

0.00456

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over