17-50370094-A-C

Position:

• chr17-50370094-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016504.3(MRPL27):​c.178T>G​(p.Tyr60Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL27 NM_016504.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.79

Genes affected

MRPL27 (HGNC:14483): (mitochondrial ribosomal protein L27) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4140029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL27	NM_016504.3	c.178T>G	p.Tyr60Asp	missense_variant	3/4	ENST00000225969.9	NP_057588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL27	ENST00000225969.9	c.178T>G	p.Tyr60Asp	missense_variant	3/4	1	NM_016504.3	ENSP00000225969.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 20, 2024

The c.178T>G (p.Y60D) alteration is located in exon 3 (coding exon 3) of the MRPL27 gene. This alteration results from a T to G substitution at nucleotide position 178, causing the tyrosine (Y) at amino acid position 60 to be replaced by an aspartic acid (D). 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	0.34
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;T;.;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	.;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	.;L;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.024	D;D;D;D;D
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.84, 1.0	.;P;.;D;.
Vest4		0.52
MutPred		0.35		.;Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);.;
MVP		0.66
MPC		0.16
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.78

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: chr17-48447455;