rs3209

chr17-47823757-T-Cchr17-47823757-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145255.4(MRPL10):c.*448A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 211,732 control chromosomes in the GnomAD database, including 10,184 homozygotes. 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: 𝑓 0.27 (6956 hom., cov: 33)
  • Exomes 𝑓: 0.31 (3228 hom.)
• Consequence: MRPL10 NM_145255.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL10	NM_145255.4	c.*448A>G		3_prime_UTR_variant	5/5	ENST00000351111.7
MRPL10	NM_148887.3	c.*448A>G		3_prime_UTR_variant	6/6
MRPL10	XM_024450575.2	c.*448A>G		3_prime_UTR_variant	6/6
MRPL10	NR_037575.2	n.1413A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL10	ENST00000351111.7	c.*448A>G		3_prime_UTR_variant	5/5	1	NM_145255.4	P1
MRPL10	ENST00000290208.11	c.*448A>G		3_prime_UTR_variant	5/5	2
MRPL10	ENST00000414011.1	c.*448A>G		3_prime_UTR_variant	6/6	3
MRPL10	ENST00000421763.5	c.*1236A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41295 AN: 152084 Hom.: 6954 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.309 AC: 18380 AN: 59530 Hom.: 3228 Cov.: 0 AF XY: 0.294 AC XY: 9404 AN XY: 31974

Gnomad4 AFR exome AF: 0.0735

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.0124

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.271 AC: 41314 AN: 152202 Hom.: 6956 Cov.: 33 AF XY: 0.270 AC XY: 20058 AN XY: 74404

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.265

Alfa AF: 0.318 Hom.: 1394

Bravo AF: 0.251

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.10
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs3209; hg19: chr17-45901123;