rs7907981

Variant names:

• chr10-27155400-T-C
• rs7907981
• NM_001172303.3:c.-27T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-27155400-T-C
• chr10-27155400-T-A
• chr10-27155400-T-G

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.-27T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,577,752 control chromosomes in the GnomAD database, including 487,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47979 hom., cov: 32)
  • Exomes 𝑓: 0.78 (439592 hom.)
• Consequence: MASTL NM_001172303.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.35
• Publications: 10 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=-0.81).
• BP6: Variant 10-27155400-T-C is Benign according to our data. Variant chr10-27155400-T-C is described in ClinVar as Benign. ClinVar VariationId is 262112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.-27T>C		5_prime_UTR	Exon 1 of 12	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.-27T>C		5_prime_UTR	Exon 1 of 13	NP_001307686.1
	MASTL	NM_001320756.2		c.-27T>C		5_prime_UTR	Exon 1 of 13	NP_001307685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.-27T>C		5_prime_UTR	Exon 1 of 12	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.-27T>C		5_prime_UTR	Exon 1 of 12	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000969651.1		c.-27T>C		5_prime_UTR	Exon 1 of 13	ENSP00000639710.1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120390 AN: 151830 Hom.: 47953 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.779

GnomAD2 exomes AF: 0.799 AC: 157070 AN: 196508 AF XY: 0.800

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.779

Gnomad EAS exome AF: 0.988

Gnomad FIN exome AF: 0.879

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.784 AC: 1117627 AN: 1425804 Hom.: 439592 Cov.: 35 AF XY: 0.785 AC XY: 554701 AN XY: 706760

African (AFR) AF: 0.793 AC: 25792 AN: 32508

American (AMR) AF: 0.717 AC: 27839 AN: 38812

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 19865 AN: 25528

East Asian (EAS) AF: 0.983 AC: 37101 AN: 37748

South Asian (SAS) AF: 0.819 AC: 68450 AN: 83544

European-Finnish (FIN) AF: 0.871 AC: 42684 AN: 49022

Middle Eastern (MID) AF: 0.765 AC: 3177 AN: 4154

European-Non Finnish (NFE) AF: 0.772 AC: 846161 AN: 1095516

Other (OTH) AF: 0.789 AC: 46558 AN: 58972

GnomAD4 genome AF: 0.793 AC: 120466 AN: 151948 Hom.: 47979 Cov.: 32 AF XY: 0.801 AC XY: 59519 AN XY: 74276

African (AFR) AF: 0.797 AC: 33068 AN: 41470

American (AMR) AF: 0.740 AC: 11310 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2696 AN: 3466

East Asian (EAS) AF: 0.987 AC: 5058 AN: 5126

South Asian (SAS) AF: 0.833 AC: 4017 AN: 4822

European-Finnish (FIN) AF: 0.879 AC: 9312 AN: 10588

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.772 AC: 52436 AN: 67884

Other (OTH) AF: 0.781 AC: 1647 AN: 2108

Alfa AF: 0.741 Hom.: 4629

Bravo AF: 0.781

Asia WGS AF: 0.884 AC: 3073 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	-0.81
CADD	Benign	0.47
DANN	Benign	0.48
PhyloP100		-4.3
PromoterAI		0.010	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: rs7907981; hg19: chr10-27444329;