7-42934967-C-T

Variant names:

• chr7-42934967-C-T
• rs769978247
• NM_031903.3:c.143C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031903.3(MRPL32):​c.143C>T​(p.Ala48Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000834 in 1,438,286 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (1 hom.)
• Consequence: MRPL32 NM_031903.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

Genes affected

MRPL32 (HGNC:14035): (mitochondrial ribosomal protein L32) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein that belongs to the L32 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome Xp. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2908641).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031903.3. 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
	MRPL32	NM_031903.3	MANE Select	c.143C>T	p.Ala48Val	missense	Exon 2 of 3	NP_114109.1	Q9BYC8
	MRPL32	NR_156497.1		n.154C>T		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL32	ENST00000223324.3	TSL:1 MANE Select	c.143C>T	p.Ala48Val	missense	Exon 2 of 3	ENSP00000223324.2	Q9BYC8
	MRPL32	ENST00000900012.1		c.143C>T	p.Ala48Val	missense	Exon 2 of 3	ENSP00000570071.1
	MRPL32	ENST00000921963.1		c.137C>T	p.Ala46Val	missense	Exon 2 of 3	ENSP00000592022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000171 AC: 4 AN: 233830 AF XY: 0.0000316

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000834 AC: 12 AN: 1438286 Hom.: 1 Cov.: 31 AF XY: 0.0000126 AC XY: 9 AN XY: 714960

African (AFR) AF: 0.00 AC: 0 AN: 32166

American (AMR) AF: 0.00 AC: 0 AN: 38474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.000134 AC: 11 AN: 82000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103448

Other (OTH) AF: 0.0000169 AC: 1 AN: 59288

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.15
Sift	Benign	0.074	T
Sift4G	Benign	0.076	T
Polyphen		0.38	B
Vest4		0.15
MutPred		0.83		Gain of sheet (P = 0.0344)
MVP		0.31
MPC		0.078
ClinPred		0.80	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.77
Mutation Taster		=76/24	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: rs769978247; hg19: chr7-42974566;