3-179604549-G-C

Position:

• chr3-179604549-G-C

Variant summary

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

The NM_177988.1(MRPL47):​c.-109C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MRPL47 NM_177988.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.478

Genes affected

MRPL47 (HGNC:16652): (mitochondrial ribosomal protein L47) 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. This gene is immediately adjacent to the gene for BAF complex 53 kDa subunit protein a (BAF53a), in a tail-to-tail orientation. Two transcript variants encoding different protein isoforms have been identified. [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=0.09577489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL47	NM_020409.3	c.76C>G	p.Pro26Ala	missense_variant	1/7	ENST00000476781.6	NP_065142.2
MRPL47	NM_177988.1	c.-109C>G		5_prime_UTR_premature_start_codon_gain_variant	1/6		NP_817125.1
MRPL47	NM_177988.1	c.-109C>G		5_prime_UTR_variant	1/6		NP_817125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL47	ENST00000392659.2	c.-109C>G		5_prime_UTR_premature_start_codon_gain_variant	1/6	1		ENSP00000376427.2
MRPL47	ENST00000476781.6	c.76C>G	p.Pro26Ala	missense_variant	1/7	1	NM_020409.3	ENSP00000417602.1
MRPL47	ENST00000259038.6	c.76C>G	p.Pro26Ala	missense_variant	1/7	1		ENSP00000259038.2
MRPL47	ENST00000392659.2	c.-109C>G		5_prime_UTR_variant	1/6	1		ENSP00000376427.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Oct 08, 2024

The c.76C>G (p.P26A) alteration is located in exon 1 (coding exon 1) of the MRPL47 gene. This alteration results from a C to G substitution at nucleotide position 76, causing the proline (P) at amino acid position 26 to be replaced by an alanine (A). 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	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.3
DANN	Benign	0.73
DEOGEN2	Benign	0.0017	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.052
Sift	Benign	0.47	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.028	B;B
Vest4		0.18
MutPred		0.38		Gain of MoRF binding (P = 0.0637);Gain of MoRF binding (P = 0.0637);
MVP		0.53
MPC		0.12
ClinPred		0.14	T
GERP RS		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-179322337;