rs2271908

Variant names:

• chr10-73252364-A-G
• rs2271908
• NM_016065.4:c.13+106T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-73252364-A-G
• chr10-73252364-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• Publications: 5 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: Benign. The variant received -20 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 VariationId is 1178938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MRPS16	NM_016065.4	c.13+106T>C		intron_variant	Intron 1 of 2	ENST00000372945.8	NP_057149.1
MRPS16	XM_047425263.1	c.-134T>C		5_prime_UTR_variant	Exon 1 of 3		XP_047281219.1
MRPS16	NM_001410935.1	c.13+106T>C		intron_variant	Intron 1 of 2		NP_001397864.1
DNAJC9-AS1	NR_038373.1	n.175+3914A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS16	ENST00000372945.8	c.13+106T>C		intron_variant	Intron 1 of 2	1	NM_016065.4	ENSP00000362036.3

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

African (AFR) AF: 0.0423 AC: 1307 AN: 30882

American (AMR) AF: 0.0764 AC: 3142 AN: 41124

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 2373 AN: 24968

East Asian (EAS) AF: 0.285 AC: 10779 AN: 37806

South Asian (SAS) AF: 0.214 AC: 17365 AN: 81246

European-Finnish (FIN) AF: 0.0449 AC: 1921 AN: 42792

Middle Eastern (MID) AF: 0.0459 AC: 206 AN: 4488

European-Non Finnish (NFE) AF: 0.0595 AC: 60631 AN: 1018764

Other (OTH) AF: 0.0817 AC: 4603 AN: 56356

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

African (AFR) AF: 0.0433 AC: 1800 AN: 41562

American (AMR) AF: 0.0715 AC: 1095 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1567 AN: 5160

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4828

European-Finnish (FIN) AF: 0.0415 AC: 441 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4013 AN: 68024

Other (OTH) AF: 0.0658 AC: 139 AN: 2112

Alfa AF: 0.0629 Hom.: 46

Bravo AF: 0.0679

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.71
PhyloP100		-1.4
PromoterAI		0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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