7-55954903-C-G

Position:

• chr7-55954903-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_015969.3(MRPS17):​c.124-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,611,772 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: MRPS17 NM_015969.3 splice_region, intron
• Scores: Splicing: ADA: 0.3994
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.657

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 7-55954903-C-G is Benign according to our data. Variant chr7-55954903-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS17	NM_015969.3	c.124-6C>G		splice_region_variant, intron_variant		ENST00000285298.9	NP_057053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS17	ENST00000285298.9	c.124-6C>G		splice_region_variant, intron_variant		1	NM_015969.3	ENSP00000285298.4
ENSG00000249773	ENST00000426595.1	c.409-6C>G		splice_region_variant, intron_variant		5		ENSP00000390331.1
MRPS17	ENST00000443449.1	c.124-6C>G		splice_region_variant, intron_variant		2		ENSP00000401349.1
NIPSNAP2	ENST00000446692.5	c.-329+2973C>G		intron_variant		4		ENSP00000406336.1

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000678 AC: 170 AN: 250560 Hom.: 1 AF XY: 0.000665 AC XY: 90 AN XY: 135376

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00134

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00136 AC: 1982 AN: 1459456 Hom.: 2 Cov.: 32 AF XY: 0.00126 AC XY: 915 AN XY: 725580

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000673

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.000896

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.000617 AC XY: 46 AN XY: 74498

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000995 Hom.: 0

Bravo AF: 0.000808

EpiCase AF: 0.00115

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

MRPS17: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.40
dbscSNV1_RF	Benign	0.41
SpliceAI score (max)		0.18		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: rs200725553; hg19: chr7-56022596;