2-75649189-A-G

Position:

• chr2-75649189-A-G

Variant summary

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

The NM_014763.4(MRPL19):​c.221+1970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,128 control chromosomes in the GnomAD database, including 27,467 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 0.60 (27467 hom., cov: 33)
• Consequence: MRPL19 NM_014763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818

Genes affected

MRPL19 (HGNC:14052): (mitochondrial ribosomal protein L19) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL19	NM_014763.4	c.221+1970A>G		intron_variant		ENST00000393909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL19	ENST00000393909.7	c.221+1970A>G		intron_variant		1	NM_014763.4	P1
MRPL19	ENST00000358788.10	c.221+1970A>G		intron_variant		5
MRPL19	ENST00000409374.5	c.221+1970A>G		intron_variant		5		P1
MRPL19	ENST00000476622.1	c.-74+1970A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90883 AN: 152008 Hom.: 27441 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.598 AC: 90954 AN: 152128 Hom.: 27467 Cov.: 33 AF XY: 0.605 AC XY: 45002 AN XY: 74396

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.588

Alfa AF: 0.588 Hom.: 14135

Bravo AF: 0.601

Asia WGS AF: 0.691 AC: 2406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.3
DANN	Benign	0.53

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: rs17689640; hg19: chr2-75876315;