17-47823757-T-G

Variant names:

• chr17-47823757-T-G
• rs3209
• NM_145255.4:c.*448A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145255.4(MRPL10):​c.*448A>C variant causes a 3 prime UTR change involving the alteration of a non-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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL10 NM_145255.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 17 publications found

Genes affected

MRPL10 (HGNC:14055): (mitochondrial ribosomal protein L10) 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 39S subunit protein. Sequence analysis identified three transcript variants that encode two different isoforms. A pseudogene corresponding to this gene is found on chromosome 5q. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL10	NM_145255.4	c.*448A>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000351111.7	NP_660298.2
MRPL10	NR_037575.2	n.1413A>C		non_coding_transcript_exon_variant	Exon 5 of 5
MRPL10	NM_148887.3	c.*448A>C		3_prime_UTR_variant	Exon 6 of 6		NP_683685.1
MRPL10	XM_024450575.2	c.*448A>C		3_prime_UTR_variant	Exon 6 of 6		XP_024306343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL10	ENST00000351111.7	c.*448A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_145255.4	ENSP00000324100.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 59754 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 32096

African (AFR) AF: 0.00 AC: 0 AN: 754

American (AMR) AF: 0.00 AC: 0 AN: 3714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1238

East Asian (EAS) AF: 0.00 AC: 0 AN: 1372

South Asian (SAS) AF: 0.00 AC: 0 AN: 11126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 35668

Other (OTH) AF: 0.00 AC: 0 AN: 3218

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.085
DANN	Benign	0.53
PhyloP100		-1.3

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

Other links and lift over

dbSNP: rs3209; hg19: chr17-45901123;