5-79988305-T-A

Position:

• chr5-79988305-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363818.2(MTX3):​c.515A>T​(p.Asp172Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTX3 NM_001363818.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

Genes affected

MTX3 (HGNC:24812): (metaxin 3) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTX3	NM_001363818.2	c.515A>T	p.Asp172Val	missense_variant	6/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2	c.332A>T	p.Asp111Val	missense_variant	5/8		NP_001161213.1
MTX3	NM_001010891.5	c.515A>T	p.Asp172Val	missense_variant	6/8		NP_001010891.4
MTX3	XM_017009440.2	c.332A>T	p.Asp111Val	missense_variant	5/7		XP_016864929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTX3	ENST00000512528.3	c.515A>T	p.Asp172Val	missense_variant	6/9	1	NM_001363818.2	ENSP00000424798.2
MTX3	ENST00000509852.6	c.515A>T	p.Asp172Val	missense_variant	6/8	1		ENSP00000423302.1
MTX3	ENST00000512560.5	c.332A>T	p.Asp111Val	missense_variant	5/8	2		ENSP00000423600.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.332A>T (p.D111V) alteration is located in exon 5 (coding exon 4) of the MTX3 gene. This alteration results from a A to T substitution at nucleotide position 332, causing the aspartic acid (D) at amino acid position 111 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.79
MutPred		0.60		Loss of ubiquitination at K174 (P = 0.1453);.;Loss of ubiquitination at K174 (P = 0.1453);
MVP		0.56
MPC		0.26
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.54
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-79284128;