5-69219666-A-G

Position:

• chr5-69219666-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033281.6(KGD4):​c.42+1795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,990 control chromosomes in the GnomAD database, including 1,045 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 0.11 (1045 hom., cov: 32)
• Consequence: KGD4 NM_033281.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

Genes affected

KGD4 (HGNC:16631): (alpha-ketoglutarate dehydrogenase subunit 4) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. The mitochondrial ribosome (mitoribosome) consists 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 28S subunit protein. Pseudogenes corresponding to this gene are found on chromosomes 3p, 4q, 8p, 11q, 12q, and 20p. [provided by RefSeq, Jul 2008]

MRPS36 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KGD4	NM_033281.6	c.42+1795A>G		intron_variant		ENST00000256441.5	NP_150597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS36	ENST00000256441.5	c.42+1795A>G		intron_variant		1	NM_033281.6	ENSP00000256441.4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16439 AN: 151872 Hom.: 1045 Cov.: 32

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.108 AC: 16437 AN: 151990 Hom.: 1045 Cov.: 32 AF XY: 0.112 AC XY: 8355 AN XY: 74276

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.0919

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.110

Alfa AF: 0.127 Hom.: 399

Bravo AF: 0.102

Asia WGS AF: 0.0520 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.33

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: rs17331590; hg19: chr5-68515493;