7-23299408-C-A

Variant names:

• chr7-23299408-C-A
• rs1459180551
• NM_138446.2:c.56C>A

Variant summary

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

The NM_138446.2(MALSU1):​c.56C>A​(p.Ala19Glu) 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. 14/20 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)
• Consequence: MALSU1 NM_138446.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.53

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

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=0.120966494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALSU1	NM_138446.2	c.56C>A	p.Ala19Glu	missense_variant	Exon 1 of 4	ENST00000466681.2	NP_612455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALSU1	ENST00000466681.2	c.56C>A	p.Ala19Glu	missense_variant	Exon 1 of 4	1	NM_138446.2	ENSP00000419370.1
MALSU1	ENST00000287543.4	n.70C>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
MALSU1	ENST00000481564.1	n.68C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
MALSU1	ENST00000479974.1	n.411+259C>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>A (p.A19E) alteration is located in exon 1 (coding exon 1) of the MALSU1 gene. This alteration results from a C to A substitution at nucleotide position 56, causing the alanine (A) at amino acid position 19 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.7
DANN	Benign	0.89
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.11
Sift	Uncertain	0.016	D
Sift4G	Benign	0.20	T
Polyphen		0.81	P
Vest4		0.30
MutPred		0.32		Gain of solvent accessibility (P = 0.0411);
MVP		0.13
MPC		0.17
ClinPred		0.20	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.071
gMVP		0.57

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

Other links and lift over

dbSNP: rs1459180551; hg19: chr7-23339027;