7-55955288-T-C

Position:

• chr7-55955288-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015969.3(MRPS17):​c.*110T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,353,814 control chromosomes in the GnomAD database, including 406,474 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51658 hom., cov: 33)
  • Exomes 𝑓: 0.77 (354816 hom.)
• Consequence: MRPS17 NM_015969.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

Genes affected

MRPS17 (HGNC:14047): (mitochondrial ribosomal protein S17) 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 S17P family. The encoded protein is moderately conserved between human mitochondrial and prokaryotic ribosomal proteins. Pseudogenes corresponding to this gene are found on chromosomes 1p, 3p, 6q, 14p, 18q, and Xq. [provided by RefSeq, Jul 2008]

NIPSNAP2 (HGNC:4179): (nipsnap homolog 2) This gene encodes a member of the NipSnap family of proteins that may be involved in vesicular transport. The encoded protein is localized to mitochondria and plays a role in oxidative phosphorylation. A pseudogene of this gene is located on the long arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS17	NM_015969.3	c.*110T>C		3_prime_UTR_variant	3/3	ENST00000285298.9	NP_057053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS17	ENST00000285298.9	c.*110T>C		3_prime_UTR_variant	3/3	1	NM_015969.3	ENSP00000285298	P1
NIPSNAP2	ENST00000446692.5	c.-329+3358T>C		intron_variant		4		ENSP00000406336

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124683 AN: 152120 Hom.: 51606 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.767 AC: 921627 AN: 1201576 Hom.: 354816 Cov.: 17 AF XY: 0.766 AC XY: 453476 AN XY: 592328

Gnomad4 AFR exome AF: 0.953

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.952

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.754

Gnomad4 OTH exome AF: 0.770

GnomAD4 genome AF: 0.820 AC: 124791 AN: 152238 Hom.: 51658 Cov.: 33 AF XY: 0.819 AC XY: 60950 AN XY: 74422

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.786

Alfa AF: 0.765 Hom.: 45284

Bravo AF: 0.826

Asia WGS AF: 0.827 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.49

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: rs15892; hg19: chr7-56022981;