NM_015969.3:c.124-6C>G

Variant names:

• chr7-55954903-C-G
• rs200725553
• NM_015969.3:c.124-6C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 2657514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015969.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS17	NM_015969.3	MANE Select	c.124-6C>G		splice_region intron	N/A	NP_057053.1	Q9Y2R5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS17	ENST00000285298.9	TSL:1 MANE Select	c.124-6C>G		splice_region intron	N/A	ENSP00000285298.4	Q9Y2R5
	ENSG00000249773	ENST00000426595.1	TSL:5	c.409-6C>G		splice_region intron	N/A	ENSP00000390331.1	I3L0E3
	MRPS17	ENST00000909935.1		c.124-6C>G		splice_region intron	N/A	ENSP00000579994.1

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

GnomAD2 exomes AF: 0.000678 AC: 170 AN: 250560 AF XY: 0.000665

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 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

African (AFR) AF: 0.000239 AC: 8 AN: 33430

American (AMR) AF: 0.0000673 AC: 3 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00171 AC: 1896 AN: 1110210

Other (OTH) AF: 0.000896 AC: 54 AN: 60290

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

African (AFR) AF: 0.000241 AC: 10 AN: 41574

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00156 AC: 106 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000995 Hom.: 0

Bravo AF: 0.000808

EpiCase AF: 0.00115

EpiControl AF: 0.00119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs200725553; hg19: chr7-56022596;