3-131468049-CAAAAAA-CAAAAAAA

Variant names:

• chr3-131468049-C-CA
• rs56928817
• NM_007208.4:c.894+41dupT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_007208.4(MRPL3):​c.894+41dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0092 (0 hom.)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

Genes affected

MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) 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 that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00922 (6605/716212) while in subpopulation EAS AF= 0.0173 (453/26250). AF 95% confidence interval is 0.0159. There are 0 homozygotes in gnomad4_exome. There are 3431 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL3	NM_007208.4	c.894+41dupT		intron_variant	Intron 9 of 9	ENST00000264995.8	NP_009139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL3	ENST00000264995.8	c.894+41_894+42insT		intron_variant	Intron 9 of 9	1	NM_007208.4	ENSP00000264995.2
MRPL3	ENST00000425847.6	c.975+41_975+42insT		intron_variant	Intron 10 of 10	2		ENSP00000398536.2
MRPL3	ENST00000511168.5	c.936+41_936+42insT		intron_variant	Intron 9 of 9	2		ENSP00000424107.1
MRPL3	ENST00000510043.1	n.318+41_318+42insT		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 221 AN: 137782 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000440

Gnomad SAS AF: 0.000239

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000466

Gnomad OTH AF: 0.00210

GnomAD3 exomes AF: 0.00437 AC: 491 AN: 112418 Hom.: 0 AF XY: 0.00483 AC XY: 300 AN XY: 62146

Gnomad AFR exome AF: 0.00620

Gnomad AMR exome AF: 0.00549

Gnomad ASJ exome AF: 0.00472

Gnomad EAS exome AF: 0.00845

Gnomad SAS exome AF: 0.00746

Gnomad FIN exome AF: 0.00295

Gnomad NFE exome AF: 0.00321

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00922 AC: 6605 AN: 716212 Hom.: 0 Cov.: 0 AF XY: 0.00930 AC XY: 3431 AN XY: 368782

Gnomad4 AFR exome AF: 0.00540

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.00780

Gnomad4 EAS exome AF: 0.0173

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.00613

Gnomad4 NFE exome AF: 0.00905

Gnomad4 OTH exome AF: 0.00900

GnomAD4 genome AF: 0.00160 AC: 221 AN: 137822 Hom.: 0 Cov.: 0 AF XY: 0.00150 AC XY: 100 AN XY: 66718

Gnomad4 AFR AF: 0.00420

Gnomad4 AMR AF: 0.00153

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000441

Gnomad4 SAS AF: 0.000240

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000466

Gnomad4 OTH AF: 0.00209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs56928817; hg19: chr3-131186893;