rs17331590

Variant names:

• chr5-69219666-A-G
• rs17331590
• NM_033281.6:c.42+1795A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

KGD4 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033281.6. 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
	KGD4	NM_033281.6	MANE Select	c.42+1795A>G		intron	N/A	NP_150597.1	P82909

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KGD4	ENST00000256441.5	TSL:1 MANE Select	c.42+1795A>G		intron	N/A	ENSP00000256441.4	P82909
	KGD4	ENST00000512880.5	TSL:5	c.-150+1551A>G		intron	N/A	ENSP00000423659.1	D6R941
	KGD4	ENST00000602380.1	TSL:2	c.-154+1555A>G		intron	N/A	ENSP00000473310.1	D6R941

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

African (AFR) AF: 0.0553 AC: 2294 AN: 41450

American (AMR) AF: 0.160 AC: 2433 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5180

South Asian (SAS) AF: 0.0919 AC: 443 AN: 4818

European-Finnish (FIN) AF: 0.188 AC: 1983 AN: 10546

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8213 AN: 67978

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.114 Hom.: 2003

Bravo AF: 0.102

Asia WGS AF: 0.0520 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.33
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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: rs17331590; hg19: chr5-68515493;