19-3797102-C-T

Position:

• chr19-3797102-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002378.4(MATK):​c.-58+4430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,920 control chromosomes in the GnomAD database, including 1,898 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 0.14 (1898 hom., cov: 31)
• Consequence: MATK NM_002378.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATK	NM_002378.4	c.-58+4430G>A		intron_variant			NP_002369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATK	ENST00000395045.6	c.-58+4430G>A		intron_variant		2		ENSP00000378485
MATK	ENST00000590849.1	c.-52+4430G>A		intron_variant		4		ENSP00000467992
MATK	ENST00000590980.1	c.-58+4430G>A		intron_variant		4		ENSP00000467472

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21864 AN: 151802 Hom.: 1896 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.144 AC: 21883 AN: 151920 Hom.: 1898 Cov.: 31 AF XY: 0.149 AC XY: 11043 AN XY: 74246

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0861

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.127

Alfa AF: 0.150 Hom.: 817

Bravo AF: 0.151

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.78

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: rs12104221; hg19: chr19-3797100;