rs2271908

chr10-73252364-A-Gchr10-73252364-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016065.4(MRPS16):c.13+106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,490,708 control chromosomes in the GnomAD database, including 6,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (619 hom., cov: 32)
  • Exomes 𝑓: 0.076 (5970 hom.)
• Consequence: MRPS16 NM_016065.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

Genes affected

MRPS16 (HGNC:14048): (mitochondrial ribosomal protein S16) 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 28S subunit protein that belongs to the ribosomal protein S16P family. The encoded protein is one of the most highly conserved ribosomal proteins between mammalian and yeast mitochondria. Three pseudogenes (located at 8q21.3, 20q13.32, 22q12-q13.1) for this gene have been described. [provided by RefSeq, Jul 2008]

DNAJC9-AS1 (HGNC:31432): (DNAJC9 and MRPS16 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-73252364-A-G is Benign according to our data. Variant chr10-73252364-A-G is described in ClinVar as [Benign]. Clinvar id is 1178938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS16	NM_016065.4	c.13+106T>C		intron_variant		ENST00000372945.8
DNAJC9-AS1	NR_038373.1	n.175+3914A>G		intron_variant, non_coding_transcript_variant
MRPS16	XM_047425263.1	c.-134T>C		5_prime_UTR_variant	1/3
MRPS16	NM_001410935.1	c.13+106T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS16	ENST00000372945.8	c.13+106T>C		intron_variant		1	NM_016065.4	P1
DNAJC9-AS1	ENST00000440197.2	n.182+3914A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10516 AN: 152164 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0627

GnomAD4 exome AF: 0.0765 AC: 102327 AN: 1338426 Hom.: 5970 Cov.: 21 AF XY: 0.0808 AC XY: 54055 AN XY: 668998

Gnomad4 AFR exome AF: 0.0423

Gnomad4 AMR exome AF: 0.0764

Gnomad4 ASJ exome AF: 0.0950

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.0449

Gnomad4 NFE exome AF: 0.0595

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.0691 AC: 10527 AN: 152282 Hom.: 619 Cov.: 32 AF XY: 0.0718 AC XY: 5345 AN XY: 74460

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0632 Hom.: 45

Bravo AF: 0.0679

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.60
Dann	Benign	0.71

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: rs2271908; hg19: chr10-75012122; COSMIC: COSV60287119; COSMIC: COSV60287119;