Variant 2-86199506-T-G 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_016622.4(MRPL35):c.16T>G(p.Phe6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MRPL35
NM_016622.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Variant links:

Genes affected

MRPL35 (HGNC:14489): (mitochondrial ribosomal protein L35) 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. Sequence analysis identified three transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 6p, 10q, and Xp. [provided by RefSeq, Jul 2008]

MRPL35 links:

Genome browser will be placed here

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=0.0053610206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPL35	NM_016622.4 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/4	ENST00000337109.9	NP_057706.2
MRPL35	NM_001363782.1 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/5		NP_001350711.1
MRPL35	NM_145644.3 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/5		NP_663619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL35	ENST00000337109.9 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/4	1	NM_016622.4	ENSP00000338389	P1	Q9NZE8-1
MRPL35	ENST00000254644.12 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/5	1		ENSP00000254644		Q9NZE8-2
MRPL35	ENST00000409180.1 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/5	3		ENSP00000386255
MRPL35	ENST00000605125.5 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	1/3	2		ENSP00000473925

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000549

AC:

138

AN:

251366

Hom.:

AF XY:

0.000471

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00301

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:

0.000229

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000209

AC:

305

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

150

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00286

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:

0.000138

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000460

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000586

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.4

DANN

Benign

0.64

DEOGEN2

Benign

0.0069

.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.0

M;.;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.18

N;.;N;N

REVEL

Benign

0.018

Sift

Uncertain

0.011

D;.;D;D

Sift4G

Benign

0.64

T;D;T;T

Polyphen

0.0040

.;.;B;.

Vest4

0.33

MVP

0.030

MPC

0.18

ClinPred

0.060

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.38

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