10-73250218-CAAAA-CAA

Variant names:

• chr10-73250218-CAA-C
• rs555061429
• NM_016065.4:c.*632_*633delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016065.4(MRPS16):​c.*632_*633delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 132,040 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 27)
  • Exomes 𝑓: 0.059 (0 hom.)
• Consequence: MRPS16 NM_016065.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS16	NM_016065.4	c.*632_*633delTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000372945.8	NP_057149.1
MRPS16	XM_047425263.1	c.*632_*633delTT		3_prime_UTR_variant	Exon 3 of 3		XP_047281219.1
MRPS16	NM_001410935.1	c.275-902_275-901delTT		intron_variant	Intron 2 of 2		NP_001397864.1
DNAJC9-AS1	NR_038373.1	n.175+1783_175+1784delAA		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS16	ENST00000372945	c.*632_*633delTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_016065.4	ENSP00000362036.3
DNAJC9-AS1	ENST00000440197.2	n.182+1783_182+1784delAA		intron_variant	Intron 2 of 3	1
MRPS16	ENST00000372940.3	c.275-902_275-901delTT		intron_variant	Intron 2 of 2	2		ENSP00000362031.3
MRPS16	ENST00000479005.1	n.1203_1204delTT		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 44 AN: 131434 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000842

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000385

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00290

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000230

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0589 AC: 33 AN: 560 Hom.: 0 AF XY: 0.0722 AC XY: 26 AN XY: 360

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0294

Gnomad4 NFE exome AF: 0.0717

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000350 AC: 46 AN: 131480 Hom.: 0 Cov.: 27 AF XY: 0.000444 AC XY: 28 AN XY: 63108

Gnomad4 AFR AF: 0.000140

Gnomad4 AMR AF: 0.000384

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000219

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00290

Gnomad4 NFE AF: 0.000230

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs555061429; hg19: chr10-75009976;