Variant 1-155208991-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002455.5(MTX1):c.187T>A(p.Ser63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,599,114 control chromosomes in the GnomAD database, including 121,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10163 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111034 hom. )

Consequence

MTX1
NM_002455.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0610

Variant links:

Genes affected

MTX1 (HGNC:7504): (metaxin 1) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

MTX1 links:

THBS3 (HGNC:11787): (thrombospondin 3) The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

THBS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002467364).

BP6

Variant 1-155208991-T-A is Benign according to our data. Variant chr1-155208991-T-A is described in ClinVar as [Benign]. Clinvar id is 767706.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTX1	NM_002455.5 linkuse as main transcript	c.187T>A	p.Ser63Thr	missense_variant	1/8	ENST00000368376.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
MTX1	ENST00000368376.8 linkuse as main transcript	c.187T>A	p.Ser63Thr	missense_variant	1/8	1	NM_002455.5	Q13505-1
MTX1	ENST00000316721.8 linkuse as main transcript	c.187T>A	p.Ser63Thr	missense_variant	1/7	1		Q13505-2
THBS3	ENST00000486260.5 linkuse as main transcript	n.61A>T		non_coding_transcript_exon_variant	1/14	5

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55030

AN:

151842

Hom.:

10154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.387

AC:

559728

AN:

1447152

Hom.:

111034

Cov.:

AF XY:

0.390

AC XY:

280180

AN XY:

718794

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.375

Gnomad4 NFE exome

AF:

0.401

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.362

AC:

55058

AN:

151962

Hom.:

10163

Cov.:

AF XY:

0.361

AC XY:

26839

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.323

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.402

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.404

Hom.:

4054

Bravo

AF:

0.347

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_noAF

Benign

-0.85

CADD

Benign

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0025

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.10

gMVP

0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over