2-75646871-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014763.4(MRPL19):c.64G>T(p.Ala22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MRPL19 NM_014763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.470

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09118819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL19	NM_014763.4	c.64G>T	p.Ala22Ser	missense_variant	1/6	ENST00000393909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL19	ENST00000393909.7	c.64G>T	p.Ala22Ser	missense_variant	1/6	1	NM_014763.4	P1
MRPL19	ENST00000409374.5	c.64G>T	p.Ala22Ser	missense_variant	1/7	5		P1
MRPL19	ENST00000358788.10	c.64G>T	p.Ala22Ser	missense_variant	1/6	5
MRPL19	ENST00000493686.1	n.89G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1444398 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 716958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.64G>T (p.A22S) alteration is located in exon 1 (coding exon 1) of the MRPL19 gene. This alteration results from a G to T substitution at nucleotide position 64, causing the alanine (A) at amino acid position 22 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	3.7
Dann	Benign	0.91
DEOGEN2	Benign	0.014	T;T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.54	T;T;.
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0070	B;.;B
Vest4		0.19
MutPred		0.29		Gain of glycosylation at A22 (P = 0.0392);Gain of glycosylation at A22 (P = 0.0392);Gain of glycosylation at A22 (P = 0.0392);
MVP		0.29
MPC		0.092
ClinPred		0.14	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.042
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-75873997;