7-55954964-T-C

Position:

• chr7-55954964-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015969.3(MRPS17):​c.179T>C​(p.Val60Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MRPS17 NM_015969.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

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]

ENSG00000249773 (HGNC:):

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS17	NM_015969.3	c.179T>C	p.Val60Ala	missense_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.179T>C	p.Val60Ala	missense_variant	3/3	1	NM_015969.3	ENSP00000285298.4
ENSG00000249773	ENST00000426595.1	c.464T>C	p.Val155Ala	missense_variant	8/8	5		ENSP00000390331.1
MRPS17	ENST00000443449.1	c.179T>C	p.Val60Ala	missense_variant	3/3	2		ENSP00000401349.1
NIPSNAP2	ENST00000446692.5	c.-329+3034T>C		intron_variant		4		ENSP00000406336.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

The c.179T>C (p.V60A) alteration is located in exon 3 (coding exon 2) of the MRPS17 gene. This alteration results from a T to C substitution at nucleotide position 179, causing the valine (V) at amino acid position 60 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	.;L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.010	D;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.39	.;B;.
Vest4		0.46
MutPred		0.55		.;Loss of stability (P = 0.0753);Loss of stability (P = 0.0753);
MVP		0.17
MPC		0.041
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.069
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-56022657;