rs192330927

Variant names:

• chr19-3778312-G-A
• rs192330927
• NM_139355.3:c.1395C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3778312-G-A
• chr19-3778312-G-C
• chr19-3778312-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_139355.3(MATK):​c.1395C>T​(p.Pro465Pro) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.02
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139355.3. 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
	MATK	NM_139355.3	MANE Select	c.1395C>T	p.Pro465Pro	synonymous	Exon 14 of 14	NP_647612.1	P42679-1
	MATK	NM_002378.4		c.1398C>T	p.Pro466Pro	synonymous	Exon 14 of 14	NP_002369.2
	MATK	NM_001440577.1		c.1395C>T	p.Pro465Pro	synonymous	Exon 14 of 14	NP_001427506.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATK	ENST00000310132.11	TSL:1 MANE Select	c.1395C>T	p.Pro465Pro	synonymous	Exon 14 of 14	ENSP00000308734.5	P42679-1
	MATK	ENST00000585778.5	TSL:1	c.1392C>T	p.Pro464Pro	synonymous	Exon 14 of 14	ENSP00000468030.1	K7EQY5
	MATK	ENST00000395040.6	TSL:1	c.1272C>T	p.Pro424Pro	synonymous	Exon 13 of 13	ENSP00000378481.1	P42679-3

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 152190 Hom.: 10 Cov.: 33

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

GnomAD2 exomes AF: 0.00493 AC: 1061 AN: 215346 AF XY: 0.00394

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 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.: 41 Cov.: 31 AF XY: 0.000878 AC XY: 620 AN XY: 706412

African (AFR) AF: 0.000541 AC: 17 AN: 31414

American (AMR) AF: 0.0382 AC: 1328 AN: 34744

Ashkenazi Jewish (ASJ) AF: 0.000165 AC: 4 AN: 24228

East Asian (EAS) AF: 0.00 AC: 0 AN: 39296

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81818

European-Finnish (FIN) AF: 0.000768 AC: 39 AN: 50764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5592

European-Non Finnish (NFE) AF: 0.0000328 AC: 36 AN: 1097278

Other (OTH) AF: 0.00109 AC: 64 AN: 58728

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152306 Hom.: 10 Cov.: 33 AF XY: 0.00345 AC XY: 257 AN XY: 74478

African (AFR) AF: 0.000433 AC: 18 AN: 41560

American (AMR) AF: 0.0261 AC: 400 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68010

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000715 Hom.: 0

Bravo AF: 0.00456

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-4.0
Mutation Taster		=100/0	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: rs192330927; hg19: chr19-3778310; COSMIC: COSV100036144; COSMIC: COSV100036144;