7-23299417-C-A

Variant names:

• chr7-23299417-C-A
• rs775114049
• NM_138446.2:c.65C>A

Variant summary

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

The NM_138446.2(MALSU1):​c.65C>A​(p.Ser22*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 1,449,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: MALSU1 NM_138446.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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>A	p.Ser22*	stop_gained	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.65C>A	p.Ser22*	stop_gained	Exon 1 of 4	ENSP00000419370.1	Q96EH3
	MALSU1	ENST00000924618.1		c.65C>A	p.Ser22*	stop_gained	Exon 1 of 4	ENSP00000594677.1
	MALSU1	ENST00000956356.1		c.65C>A	p.Ser22*	stop_gained	Exon 1 of 2	ENSP00000626415.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000533 AC: 12 AN: 225104 AF XY: 0.0000321

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000897 AC: 13 AN: 1449296 Hom.: 0 Cov.: 31 AF XY: 0.00000555 AC XY: 4 AN XY: 720884

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.000292 AC: 13 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.00 AC: 0 AN: 85792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5042

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110062

Other (OTH) AF: 0.00 AC: 0 AN: 59956

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000335 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	30
DANN	Benign	0.93
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.035	N
PhyloP100		-0.85
Vest4		0.024
GERP RS		-1.9
PromoterAI		-0.22	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.2
Mutation Taster		=38/162	disease causing (fs/PTC)

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: rs775114049; hg19: chr7-23339036;