6-44114201-C-T

Position:

• chr6-44114201-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032111.4(MRPL14):​c.80G>A​(p.Gly27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL14 NM_032111.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42

Genes affected

MRPL14 (HGNC:14279): (mitochondrial ribosomal protein L14) This nuclear gene encodes a protein component of the 39S subunit of the mitochondrial ribosome. A pseudogene of this gene is found on chromosome 17. [provided by RefSeq, Jan 2016]

POLR1C (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063843966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL14	NM_032111.4	c.80G>A	p.Gly27Glu	missense_variant	3/3	ENST00000372014.5	NP_115487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL14	ENST00000372014.5	c.80G>A	p.Gly27Glu	missense_variant	3/3	1	NM_032111.4	ENSP00000361084	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 23, 2023

The c.80G>A (p.G27E) alteration is located in exon 3 (coding exon 2) of the MRPL14 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the glycine (G) at amino acid position 27 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.035
Sift	Benign	0.31	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.31		Gain of solvent accessibility (P = 0.012);
MVP		0.24
MPC		0.27
ClinPred		0.071	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.52

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: rs1775613555; hg19: chr6-44081938;