Variant 11-59809903-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017840.4(MRPL16):c.73C>T(p.Pro25Ser) 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. 14/21 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL16
NM_017840.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.327

Variant links:

Genes affected

MRPL16 (HGNC:14476): (mitochondrial ribosomal protein L16) 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]

MRPL16 links:

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ACMG classification

Classification made for transcript

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=0.061608642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL16	NM_017840.4 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	2/4	ENST00000300151.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MRPL16	ENST00000300151.5 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	2/4	1	NM_017840.4	P1
MRPL16	ENST00000534340.1 linkuse as main transcript	c.-237C>T		5_prime_UTR_variant	2/4	3
MRPL16	ENST00000525470.1 linkuse as main transcript	n.120C>T		non_coding_transcript_exon_variant	1/3	5
MRPL16	ENST00000531802.1 linkuse as main transcript	n.188C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250726

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726814

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.58

M_CAP

Benign

0.0036

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.16

REVEL

Benign

0.044

Sift

Benign

0.87

Sift4G

Benign

0.78

Polyphen

0.0010

Vest4

0.19

MutPred

0.41

Gain of helix (P = 0.0128);

MVP

0.31

MPC

0.12

ClinPred

0.043

GERP RS

1.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.031

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over