rs7068375

Variant names:

• chr10-27165182-A-T
• rs7068375
• NM_001172303.3:c.660+12A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-27165182-A-T
• chr10-27165182-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001172303.3(MASTL):​c.660+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,577,492 control chromosomes in the GnomAD database, including 309,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27731 hom., cov: 30)
  • Exomes 𝑓: 0.62 (281610 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.21
• Publications: 18 publications found

Genes affected

MASTL (HGNC:19042): (microtubule associated serine/threonine kinase like) This gene encodes a microtubule-associated serine/threonine kinase. Mutations at this locus have been associated with autosomal dominant thrombocytopenia, also known as thrombocytopenia-2. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Feb 2010]

MASTL Gene-Disease associations (from GenCC):

• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thrombocytopenia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-27165182-A-T is Benign according to our data. Variant chr10-27165182-A-T is described in ClinVar as Benign. ClinVar VariationId is 262126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172303.3. 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
	MASTL	NM_001172303.3	MANE Select	c.660+12A>T		intron	N/A	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.660+12A>T		intron	N/A	NP_001307686.1
	MASTL	NM_001320756.2		c.660+12A>T		intron	N/A	NP_001307685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.660+12A>T		intron	N/A	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.660+12A>T		intron	N/A	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000969651.1		c.660+12A>T		intron	N/A	ENSP00000639710.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91263 AN: 151778 Hom.: 27737 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.593

GnomAD2 exomes AF: 0.591 AC: 148154 AN: 250732 AF XY: 0.590

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.434

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.650

Gnomad OTH exome AF: 0.617

GnomAD4 exome AF: 0.625 AC: 890655 AN: 1425596 Hom.: 281610 Cov.: 26 AF XY: 0.621 AC XY: 442201 AN XY: 711538

African (AFR) AF: 0.554 AC: 18093 AN: 32664

American (AMR) AF: 0.537 AC: 24000 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 16021 AN: 25900

East Asian (EAS) AF: 0.398 AC: 15707 AN: 39468

South Asian (SAS) AF: 0.492 AC: 42024 AN: 85450

European-Finnish (FIN) AF: 0.661 AC: 35264 AN: 53350

Middle Eastern (MID) AF: 0.579 AC: 3293 AN: 5690

European-Non Finnish (NFE) AF: 0.649 AC: 700070 AN: 1079212

Other (OTH) AF: 0.611 AC: 36183 AN: 59196

GnomAD4 genome AF: 0.601 AC: 91267 AN: 151896 Hom.: 27731 Cov.: 30 AF XY: 0.600 AC XY: 44502 AN XY: 74210

African (AFR) AF: 0.553 AC: 22887 AN: 41410

American (AMR) AF: 0.570 AC: 8703 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2180 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2188 AN: 5148

South Asian (SAS) AF: 0.479 AC: 2305 AN: 4814

European-Finnish (FIN) AF: 0.662 AC: 6962 AN: 10518

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44067 AN: 67946

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.627 Hom.: 5573

Bravo AF: 0.593

Asia WGS AF: 0.443 AC: 1542 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs7068375; hg19: chr10-27454111; COSMIC: COSV60909955; COSMIC: COSV60909955;