chr7-23299401-C-T

Variant names:

• chr7-23299401-C-T
• rs371357761
• NM_138446.2:c.49C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138446.2(MALSU1):​c.49C>T​(p.Arg17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,598,924 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00038 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: MALSU1 NM_138446.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0490
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023763537).

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.49C>T	p.Arg17Cys	missense	Exon 1 of 4	NP_612455.1	Q96EH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALSU1	ENST00000466681.2	TSL:1 MANE Select	c.49C>T	p.Arg17Cys	missense	Exon 1 of 4	ENSP00000419370.1	Q96EH3
	MALSU1	ENST00000924618.1		c.49C>T	p.Arg17Cys	missense	Exon 1 of 4	ENSP00000594677.1
	MALSU1	ENST00000956356.1		c.49C>T	p.Arg17Cys	missense	Exon 1 of 2	ENSP00000626415.1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000291 AC: 65 AN: 222988 AF XY: 0.000291

Gnomad AFR exome AF: 0.000151

Gnomad AMR exome AF: 0.0000590

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000574

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000410

Gnomad OTH exome AF: 0.000357

GnomAD4 exome AF: 0.000415 AC: 600 AN: 1446564 Hom.: 1 Cov.: 31 AF XY: 0.000417 AC XY: 300 AN XY: 719500

African (AFR) AF: 0.0000600 AC: 2 AN: 33316

American (AMR) AF: 0.0000901 AC: 4 AN: 44410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.000759 AC: 65 AN: 85648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4744

European-Non Finnish (NFE) AF: 0.000468 AC: 519 AN: 1109630

Other (OTH) AF: 0.000167 AC: 10 AN: 59860

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29 AN XY: 74512

African (AFR) AF: 0.000192 AC: 8 AN: 41594

American (AMR) AF: 0.000457 AC: 7 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000513 Hom.: 0

Bravo AF: 0.000370

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000359 AC: 3

ExAC AF: 0.000260 AC: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.049
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.045
Sift	Benign	0.079	T
Sift4G	Benign	0.087	T
Polyphen		0.029	B
Vest4		0.21
MVP		0.14
MPC		0.081
ClinPred		0.024	T
GERP RS		0.48
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.075
gMVP		0.48
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs371357761; hg19: chr7-23339020;