2-223957952-T-C

Position:

• chr2-223957952-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022915.5(MRPL44):​c.179+301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,894 control chromosomes in the GnomAD database, including 15,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15274 hom., cov: 32)
• Consequence: MRPL44 NM_022915.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.92

Genes affected

MRPL44 (HGNC:16650): (mitochondrial ribosomal protein L44) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-223957952-T-C is Benign according to our data. Variant chr2-223957952-T-C is described in ClinVar as [Benign]. Clinvar id is 682628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL44	NM_022915.5	c.179+301T>C		intron_variant		ENST00000258383.4
MRPL44	XM_011511668.3	c.138-1582T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL44	ENST00000258383.4	c.179+301T>C		intron_variant		1	NM_022915.5	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67914 AN: 151776 Hom.: 15250 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.448 AC: 67980 AN: 151894 Hom.: 15274 Cov.: 32 AF XY: 0.445 AC XY: 33066 AN XY: 74240

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.426

Alfa AF: 0.415 Hom.: 6905

Bravo AF: 0.449

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.83
DANN	Benign	0.41

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: rs1347818; hg19: chr2-224822669;