10-73424615-G-A

Position:

• chr10-73424615-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024593.2(MSS51):​c.1321C>T​(p.Leu441Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: MSS51 NM_001024593.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17618859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSS51	NM_001024593.2	c.1321C>T	p.Leu441Phe	missense_variant	7/7	ENST00000299432.7	NP_001019764.1
MSS51	XM_047424550.1	c.1321C>T	p.Leu441Phe	missense_variant	6/6		XP_047280506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSS51	ENST00000299432.7	c.1321C>T	p.Leu441Phe	missense_variant	7/7	1	NM_001024593.2	ENSP00000299432	P1
MSS51	ENST00000372912.1	c.1321C>T	p.Leu441Phe	missense_variant	6/6	1		ENSP00000362003	P1
MSS51	ENST00000487126.5	c.*344C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	2		ENSP00000435203

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 29, 2022

The c.1321C>T (p.L441F) alteration is located in exon 7 (coding exon 6) of the MSS51 gene. This alteration results from a C to T substitution at nucleotide position 1321, causing the leucine (L) at amino acid position 441 to be replaced by a phenylalanine (F). 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	0.090
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.85	D;D
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.028
Sift	Benign	0.70	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.014	B;B
Vest4		0.22
MutPred		0.24		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.27
MPC		0.23
ClinPred		0.64	D
GERP RS		4.7
Varity_R		0.10
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-75184373;