Variant 10-73426009-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001024593.2(MSS51):c.871C>T(p.Pro291Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MSS51
NM_001024593.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

Variant links:

Genes affected

MSS51 (HGNC:21000): (MSS51 mitochondrial translational activator) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

MSS51 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41713965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSS51	NM_001024593.2 linkuse as main transcript	c.871C>T	p.Pro291Ser	missense_variant	5/7	ENST00000299432.7	NP_001019764.1
MSS51	XM_047424550.1 linkuse as main transcript	c.871C>T	p.Pro291Ser	missense_variant	4/6		XP_047280506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSS51	ENST00000299432.7 linkuse as main transcript	c.871C>T	p.Pro291Ser	missense_variant	5/7	1	NM_001024593.2	ENSP00000299432	P1	Q4VC12-1
MSS51	ENST00000372912.1 linkuse as main transcript	c.871C>T	p.Pro291Ser	missense_variant	4/6	1		ENSP00000362003	P1	Q4VC12-1
MSS51	ENST00000487126.5 linkuse as main transcript	c.503-63C>T		intron_variant, NMD_transcript_variant		2		ENSP00000435203

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251452

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000110

AC:

161

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000112

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.871C>T (p.P291S) 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 871, causing the proline (P) at amino acid position 291 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

T;.

M_CAP

Benign

0.034

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

0.99

D;D

Vest4

0.46

MVP

0.60

MPC

0.27

ClinPred

0.21

GERP RS

3.6

Varity_R

0.22

gMVP

0.79

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

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