17-47823757-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRPL10	NM_145255.4	c.*448A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000351111.7	NP_660298.2
MRPL10	NR_037575.2	n.1413A>G		non_coding_transcript_exon_variant	Exon 5 of 5
MRPL10	NM_148887.3	c.*448A>G		3_prime_UTR_variant	Exon 6 of 6		NP_683685.1
MRPL10	XM_024450575.2	c.*448A>G		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>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_145255.4	ENSP00000324100.4

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

African (AFR) AF: 0.0735 AC: 55 AN: 748

American (AMR) AF: 0.216 AC: 801 AN: 3708

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 399 AN: 1236

East Asian (EAS) AF: 0.0124 AC: 17 AN: 1372

South Asian (SAS) AF: 0.219 AC: 2430 AN: 11094

European-Finnish (FIN) AF: 0.396 AC: 959 AN: 2422

Middle Eastern (MID) AF: 0.333 AC: 76 AN: 228

European-Non Finnish (NFE) AF: 0.354 AC: 12575 AN: 35512

Other (OTH) AF: 0.333 AC: 1068 AN: 3210

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

African (AFR) AF: 0.112 AC: 4653 AN: 41534

American (AMR) AF: 0.219 AC: 3346 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3470

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5180

South Asian (SAS) AF: 0.220 AC: 1064 AN: 4834

European-Finnish (FIN) AF: 0.403 AC: 4259 AN: 10580

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25795 AN: 67988

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.312 Hom.: 1402

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
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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;