7-42940272-A-T

Variant names:

• chr7-42940272-A-T
• rs674462
• ENST00000496564.1:n.94+5136A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000496564.1(MRPL32):​n.94+5136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,122 control chromosomes in the GnomAD database, including 27,046 homozygotes. 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: 𝑓 0.58 (27046 hom., cov: 33)
• Consequence: MRPL32 ENST00000496564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL32	ENST00000496564.1	n.94+5136A>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88610 AN: 152004 Hom.: 27045 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.583 AC: 88636 AN: 152122 Hom.: 27046 Cov.: 33 AF XY: 0.590 AC XY: 43870 AN XY: 74378

African (AFR) AF: 0.409 AC: 16962 AN: 41484

American (AMR) AF: 0.603 AC: 9220 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2097 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4080 AN: 5176

South Asian (SAS) AF: 0.614 AC: 2961 AN: 4824

European-Finnish (FIN) AF: 0.760 AC: 8047 AN: 10594

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.638 AC: 43355 AN: 67972

Other (OTH) AF: 0.544 AC: 1150 AN: 2114

Alfa AF: 0.516 Hom.: 1723

Bravo AF: 0.562

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.29
PhyloP100		0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs674462; hg19: chr7-42979871;