rs2829806

chr21-25587877-T-G

Variant summary

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

The NM_017446.4(MRPL39):c.969+958A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 970,970 control chromosomes in the GnomAD database, including 231,300 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 0.62 (31273 hom., cov: 32)
  • Exomes 𝑓: 0.68 (200027 hom.)
• Consequence: MRPL39 NM_017446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

MRPL39 (HGNC:14027): (mitochondrial ribosomal protein L39) 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. Two transcript variants encoding distinct isoforms have been described. A pseudogene corresponding to this gene is found on chromosome 5q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL39	NM_017446.4	c.969+958A>C		intron_variant		ENST00000352957.9
MRPL39	NM_080794.4	c.970-88A>C		intron_variant
MRPL39	XM_006724026.5	c.970-88A>C		intron_variant
MRPL39	XM_011529651.3	c.843+958A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL39	ENST00000352957.9	c.969+958A>C		intron_variant		1	NM_017446.4	P1
MRPL39	ENST00000307301.11	c.970-88A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94592 AN: 151930 Hom.: 31272 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.666

GnomAD4 exome AF: 0.681 AC: 557361 AN: 818922 Hom.: 200027 AF XY: 0.675 AC XY: 288130 AN XY: 426982

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.823

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.754

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.622 AC: 94619 AN: 152048 Hom.: 31273 Cov.: 32 AF XY: 0.613 AC XY: 45584 AN XY: 74358

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.660

Alfa AF: 0.707 Hom.: 17832

Bravo AF: 0.608

Asia WGS AF: 0.320 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.13
Dann	Benign	0.55

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: rs2829806; hg19: chr21-26960189; COSMIC: COSV56260810; COSMIC: COSV56260810;