Variant 10-73250218-C-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_016065.4(MRPS16):c.*633_*634insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 132,152 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0054 ( 11 hom., cov: 27)

Exomes 𝑓: 0.049 ( 0 hom. )

Consequence

MRPS16
NM_016065.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0840

Variant links:

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]

MRPS16 links:

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

DNAJC9-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00535 (704/131576) while in subpopulation EAS AF= 0.0518 (236/4556). AF 95% confidence interval is 0.0464. There are 11 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MRPS16	NM_016065.4 linkuse as main transcript	c.633_634insT	3_prime_UTR_variant	3/3	ENST00000372945.8
DNAJC9-AS1	NR_038373.1 linkuse as main transcript	n.175+1784dup	intron_variant, non_coding_transcript_variant
MRPS16	XM_047425263.1 linkuse as main transcript	c.633_634insT	3_prime_UTR_variant	3/3
MRPS16	NM_001410935.1 linkuse as main transcript	c.275-901_275-900insT	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS16	ENST00000372945.8 linkuse as main transcript	c.633_634insT	3_prime_UTR_variant	3/3	1	NM_016065.4	P1	Q9Y3D3-1
DNAJC9-AS1	ENST00000440197.2 linkuse as main transcript	n.182+1784dup	intron_variant, non_coding_transcript_variant		1
MRPS16	ENST00000372940.3 linkuse as main transcript	c.275-901_275-900insT	intron_variant		2
MRPS16	ENST00000479005.1 linkuse as main transcript	n.1204_1205insT	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

706

AN:

131526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00119

Gnomad AMR

AF:

0.00592

Gnomad ASJ

AF:

0.000313

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.00591

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.00357

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00902

GnomAD4 exome

AF:

0.0486

AC:

AN:

576

Hom.:

Cov.:

AF XY:

0.0511

AC XY:

AN XY:

372

show subpopulations

Gnomad4 AMR exome

AF:

0.0600

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0625

Gnomad4 SAS exome

AF:

0.0294

Gnomad4 NFE exome

AF:

0.0502

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00535

AC:

704

AN:

131576

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

418

AN XY:

63178

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00591

Gnomad4 ASJ

AF:

0.000313

Gnomad4 EAS

AF:

0.0518

Gnomad4 SAS

AF:

0.00593

Gnomad4 FIN

AF:

0.0238

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.00895

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over