10-73425822-G-A

Position:

• chr10-73425822-G-A

Variant summary

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

The ENST00000299432.7(MSS51):​c.1058C>T​(p.Ala353Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MSS51 ENST00000299432.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

Genes affected

MSS51 (HGNC:21000): (MSS51 mitochondrial translational activator) Predicted to enable metal ion binding activity. [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
MSS51	NM_001024593.2	c.1058C>T	p.Ala353Val	missense_variant	5/7	ENST00000299432.7	NP_001019764.1
MSS51	XM_047424550.1	c.1058C>T	p.Ala353Val	missense_variant	4/6		XP_047280506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSS51	ENST00000299432.7	c.1058C>T	p.Ala353Val	missense_variant	5/7	1	NM_001024593.2	ENSP00000299432.2
MSS51	ENST00000372912.1	c.1058C>T	p.Ala353Val	missense_variant	4/6	1		ENSP00000362003.1
MSS51	ENST00000487126.5	n.*81C>T		non_coding_transcript_exon_variant	5/7	2		ENSP00000435203.1
MSS51	ENST00000487126.5	n.*81C>T		3_prime_UTR_variant	5/7	2		ENSP00000435203.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460486 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 17, 2024

The c.1058C>T (p.A353V) alteration is located in exon 5 (coding exon 4) of the MSS51 gene. This alteration results from a C to T substitution at nucleotide position 1058, causing the alanine (A) at amino acid position 353 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	Benign	0.26
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;.
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.96	D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.36	B;B
Vest4		0.61
MutPred		0.51		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.58
MPC		0.14
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.085
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2055980957; hg19: chr10-75185580; COSMIC: COSV55019521; COSMIC: COSV55019521;