3-131469533-T-TAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007208.4(MRPL3):c.816+162_816+163insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.032 (84 hom., cov: 0)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 3-131469533-T-TAC is Benign according to our data. Variant chr3-131469533-T-TAC is described in ClinVar as [Likely_benign]. Clinvar id is 1198044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0325 (4771/146964) while in subpopulation SAS AF= 0.0514 (238/4626). AF 95% confidence interval is 0.0461. There are 84 homozygotes in gnomad4. There are 2364 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 83 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4	c.816+162_816+163insGT		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8	c.816+162_816+163insGT		intron_variant		1	NM_007208.4	P1
MRPL3	ENST00000425847.6	c.897+162_897+163insGT		intron_variant		2
MRPL3	ENST00000511168.5	c.859+162_859+163insGT		intron_variant		2
MRPL3	ENST00000510043.1	n.240+162_240+163insGT		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4768 AN: 146852 Hom.: 83 Cov.: 0

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0831

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0417

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0400

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0325 AC: 4771 AN: 146964 Hom.: 84 Cov.: 0 AF XY: 0.0330 AC XY: 2364 AN XY: 71678

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.0417

Gnomad4 EAS AF: 0.0385

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0305

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3830301; hg19: chr3-131188377;