rs760077

Positions:

• chr1-155208991-T-A
• chr1-155208991-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610

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]

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]

ACMG classification

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	Protein	UniProt
MTX1	NM_002455.5	c.187T>A	p.Ser63Thr	missense_variant	1/8	ENST00000368376.8	NP_002446.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTX1	ENST00000368376.8	c.187T>A	p.Ser63Thr	missense_variant	1/8	1	NM_002455.5	ENSP00000357360
MTX1	ENST00000316721.8	c.187T>A	p.Ser63Thr	missense_variant	1/7	1		ENSP00000317106
THBS3	ENST00000486260.5	n.61A>T		non_coding_transcript_exon_variant	1/14	5

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55030 AN: 151842 Hom.: 10154 Cov.: 32

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.: 73 AF XY: 0.390 AC XY: 280180 AN XY: 718794

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.: 32 AF XY: 0.361 AC XY: 26839 AN XY: 74274

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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	14
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

Other links and lift over

dbSNP: rs760077; hg19: chr1-155178782;