NM_016065.4:c.*633dupT

Variant names:

• chr10-73250218-C-CA
• rs555061429
• NM_016065.4:c.*633dupT

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_016065.4(MRPS16):​c.*633dupT 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0840
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016065.4. 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
	MRPS16	NM_016065.4	MANE Select	c.*633dupT		3_prime_UTR	Exon 3 of 3	NP_057149.1	Q9Y3D3-1
	MRPS16	NM_001410935.1		c.275-901dupT		intron	N/A	NP_001397864.1	A6ND22
	DNAJC9-AS1	NR_038373.1		n.175+1784dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS16	ENST00000372945.8	TSL:1 MANE Select	c.*633dupT		3_prime_UTR	Exon 3 of 3	ENSP00000362036.3	Q9Y3D3-1
	DNAJC9-AS1	ENST00000440197.2	TSL:1	n.182+1784dupA		intron	N/A
	MRPS16	ENST00000372940.3	TSL:2	c.275-901dupT		intron	N/A	ENSP00000362031.3	A6ND22

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 706 AN: 131526 Hom.: 11 Cov.: 27

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: 28 AN: 576 Hom.: 0 Cov.: 0 AF XY: 0.0511 AC XY: 19 AN XY: 372

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.0600 AC: 3 AN: 50

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.0625 AC: 1 AN: 16

South Asian (SAS) AF: 0.0294 AC: 1 AN: 34

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0502 AC: 23 AN: 458

Other (OTH) AF: 0.00 AC: 0 AN: 16

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000410783), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00535 AC: 704 AN: 131576 Hom.: 11 Cov.: 27 AF XY: 0.00662 AC XY: 418 AN XY: 63178

African (AFR) AF: 0.00173 AC: 62 AN: 35736

American (AMR) AF: 0.00591 AC: 77 AN: 13018

Ashkenazi Jewish (ASJ) AF: 0.000313 AC: 1 AN: 3190

East Asian (EAS) AF: 0.0518 AC: 236 AN: 4556

South Asian (SAS) AF: 0.00593 AC: 24 AN: 4048

European-Finnish (FIN) AF: 0.0238 AC: 173 AN: 7280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00187 AC: 114 AN: 60866

Other (OTH) AF: 0.00895 AC: 16 AN: 1788

Alfa AF: 0.00326 Hom.: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Combined oxidative phosphorylation deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.084
Mutation Taster		=100/0	polymorphism

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: rs555061429; hg19: chr10-75009976;