Genetic Variant NM_138446.2:c.65C>T (chr7-23299417-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138446.2(MALSU1):c.65C>T(p.Ser22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,601,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MALSU1
NM_138446.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.852

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07420096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138446.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALSU1	NM_138446.2	MANE Select	c.65C>T	p.Ser22Leu	missense	Exon 1 of 4	NP_612455.1	Q96EH3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MALSU1	ENST00000466681.2	TSL:1 MANE Select	c.65C>T	p.Ser22Leu	missense	Exon 1 of 4	ENSP00000419370.1	Q96EH3
MALSU1	ENST00000924618.1		c.65C>T	p.Ser22Leu	missense	Exon 1 of 4	ENSP00000594677.1
MALSU1	ENST00000956356.1		c.65C>T	p.Ser22Leu	missense	Exon 1 of 2	ENSP00000626415.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225104

AF XY:

0.00000803

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1449296

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720884

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

85792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5042

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110062

Other (OTH)

AF:

0.00

AC:

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.48

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.041

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.59

M_CAP

Benign

0.0070

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

-0.85

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.85

REVEL

Benign

0.044

Sift

Benign

0.23

Sift4G

Benign

0.19

Polyphen

0.16

Vest4

0.13

MutPred

0.27

Loss of disorder (P = 0.0202)

MVP

0.13

MPC

0.058

ClinPred

0.076

GERP RS

-1.9

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.2

Varity_R

0.039

gMVP

0.28

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over