rs7919803

Variant names:

• chr10-27155399-C-A
• rs7919803
• NM_001172303.3:c.-28C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27155399-C-A
• chr10-27155399-C-T

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.-28C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,575,846 control chromosomes in the GnomAD database, including 309,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27801 hom., cov: 32)
  • Exomes 𝑓: 0.63 (282083 hom.)
• Consequence: MASTL NM_001172303.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.224
• Publications: 15 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]

YME1L1 (HGNC:12843): (YME1 like 1 ATPase) The protein encoded by this gene is the human ortholog of yeast mitochondrial AAA metalloprotease, Yme1p. It is localized in the mitochondria and can functionally complement a yme1 disruptant yeast strain. It is proposed that this gene plays a role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

YME1L1 Gene-Disease associations (from GenCC):

• autosomal recessive optic atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• optic atrophy 11

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-27155399-C-A is Benign according to our data. Variant chr10-27155399-C-A is described in ClinVar as Benign. ClinVar VariationId is 262113.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.-28C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001165774.1	Q96GX5-1
	MASTL	NM_001172303.3	MANE Select	c.-28C>A		5_prime_UTR	Exon 1 of 12	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.-28C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001307686.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.-28C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.-28C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.-28C>A		5_prime_UTR	Exon 1 of 12	ENSP00000365107.5	Q96GX5-1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91400 AN: 151786 Hom.: 27804 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.592

GnomAD2 exomes AF: 0.592 AC: 115272 AN: 194594 AF XY: 0.590

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.541

Gnomad ASJ exome AF: 0.616

Gnomad EAS exome AF: 0.441

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.653

Gnomad OTH exome AF: 0.625

GnomAD4 exome AF: 0.626 AC: 891481 AN: 1423946 Hom.: 282083 Cov.: 33 AF XY: 0.623 AC XY: 439517 AN XY: 705682

African (AFR) AF: 0.559 AC: 18118 AN: 32424

American (AMR) AF: 0.541 AC: 20911 AN: 38620

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 15787 AN: 25480

East Asian (EAS) AF: 0.399 AC: 14986 AN: 37538

South Asian (SAS) AF: 0.492 AC: 41022 AN: 83338

European-Finnish (FIN) AF: 0.663 AC: 32384 AN: 48818

Middle Eastern (MID) AF: 0.592 AC: 2458 AN: 4152

European-Non Finnish (NFE) AF: 0.648 AC: 709780 AN: 1094676

Other (OTH) AF: 0.612 AC: 36035 AN: 58900

GnomAD4 genome AF: 0.602 AC: 91406 AN: 151900 Hom.: 27801 Cov.: 32 AF XY: 0.601 AC XY: 44600 AN XY: 74238

African (AFR) AF: 0.556 AC: 23070 AN: 41460

American (AMR) AF: 0.570 AC: 8704 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2179 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2181 AN: 5116

South Asian (SAS) AF: 0.479 AC: 2308 AN: 4820

European-Finnish (FIN) AF: 0.662 AC: 6999 AN: 10574

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.648 AC: 43993 AN: 67878

Other (OTH) AF: 0.585 AC: 1234 AN: 2110

Alfa AF: 0.626 Hom.: 5623

Bravo AF: 0.594

Asia WGS AF: 0.445 AC: 1549 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	-0.74
CADD	Benign	8.0
DANN	Benign	0.72
PhyloP100		0.22
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs7919803; hg19: chr10-27444328; COSMIC: COSV58759031; COSMIC: COSV58759031;