7-55953308-A-T

Variant names:

• chr7-55953308-A-T
• rs546835814
• NM_015969.3:c.113A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015969.3(MRPS17):​c.113A>T​(p.Tyr38Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MRPS17 NM_015969.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.79

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3609533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS17	NM_015969.3	c.113A>T	p.Tyr38Phe	missense_variant	Exon 2 of 3	ENST00000285298.9	NP_057053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS17	ENST00000285298.9	c.113A>T	p.Tyr38Phe	missense_variant	Exon 2 of 3	1	NM_015969.3	ENSP00000285298.4
ENSG00000249773	ENST00000426595.1	c.398A>T	p.Tyr133Phe	missense_variant	Exon 7 of 8	5		ENSP00000390331.1
MRPS17	ENST00000443449.1	c.113A>T	p.Tyr38Phe	missense_variant	Exon 2 of 3	2		ENSP00000401349.1
NIPSNAP2	ENST00000446692.5	c.-329+1378A>T		intron_variant	Intron 1 of 6	4		ENSP00000406336.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.2	.;L;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N;D;D
REVEL	Benign	0.23
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.70	.;P;.
Vest4		0.58
MutPred		0.26		.;Gain of methylation at K41 (P = 0.0805);Gain of methylation at K41 (P = 0.0805);
MVP		0.22
MPC		0.045
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.14
gMVP		0.46

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: rs546835814; hg19: chr7-56021001;