Variant 7-23299474-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138446.2(MALSU1):c.122G>C(p.Arg41Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MALSU1
NM_138446.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

MALSU1 (HGNC:21721): (mitochondrial assembly of ribosomal large subunit 1) Predicted to enable ribosomal large subunit binding activity. Involved in negative regulation of mitochondrial translation and ribosomal large subunit biogenesis. Located in cytosol and mitochondrion. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MALSU1 links:

MALSU1 (HGNC:):

MALSU1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.19525605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MALSU1	NM_138446.2 linkuse as main transcript	c.122G>C	p.Arg41Pro	missense_variant	1/4	ENST00000466681.2	NP_612455.1	Q96EH3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MALSU1	ENST00000466681.2 linkuse as main transcript	c.122G>C	p.Arg41Pro	missense_variant	1/4	1	NM_138446.2	ENSP00000419370.1	Q96EH3
MALSU1	ENST00000287543.4 linkuse as main transcript	n.136G>C		non_coding_transcript_exon_variant	1/3	2
MALSU1	ENST00000481564.1 linkuse as main transcript	n.134G>C		non_coding_transcript_exon_variant	1/2	2
MALSU1	ENST00000479974.1 linkuse as main transcript	n.411+325G>C		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000848

AC:

AN:

235794

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1457736

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725364

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000566

Hom.:

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

Dec 13, 2022

The c.122G>C (p.R41P) alteration is located in exon 1 (coding exon 1) of the MALSU1 gene. This alteration results from a G to C substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a proline (P). 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

0.084

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.050

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.50

M_CAP

Benign

0.034

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.2

REVEL

Benign

0.10

Sift

Benign

0.033

Sift4G

Uncertain

0.042

Polyphen

0.93

Vest4

0.39

MutPred

0.46

Gain of relative solvent accessibility (P = 0.005);

MVP

0.32

MPC

0.088

ClinPred

0.70

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.23

gMVP

0.47

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