Genetic Variant CLUH:p.Gly1330Arg (chr17-2690653-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366661.1(CLUH):c.3988G>A(p.Gly1330Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLUH
NM_001366661.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.757

Publications

0 publications found

Variant links:

Genes affected

CLUH (HGNC:29094): (clustered mitochondria homolog) Enables mRNA binding activity. Involved in intracellular distribution of mitochondria. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CLUH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12346801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366661.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLUH	NM_001366661.1	MANE Select	c.3988G>A	p.Gly1330Arg	missense	Exon 26 of 26	NP_001353590.1	A0A494C0R8
CLUH	NM_015229.4		c.3985G>A	p.Gly1329Arg	missense	Exon 26 of 26	NP_056044.4
CLUH	NM_001366662.1		c.3871G>A	p.Gly1291Arg	missense	Exon 26 of 26	NP_001353591.1	O75153

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLUH	ENST00000651024.2	MANE Select	c.3988G>A	p.Gly1330Arg	missense	Exon 26 of 26	ENSP00000498679.1	A0A494C0R8
CLUH	ENST00000876318.1		c.4006G>A	p.Gly1336Arg	missense	Exon 26 of 26	ENSP00000546377.1
CLUH	ENST00000876317.1		c.4003G>A	p.Gly1335Arg	missense	Exon 26 of 26	ENSP00000546376.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1386182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688378

African (AFR)

AF:

0.00

AC:

AN:

28504

American (AMR)

AF:

0.00

AC:

AN:

29570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22540

East Asian (EAS)

AF:

0.00

AC:

AN:

34802

South Asian (SAS)

AF:

0.00

AC:

AN:

76248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081510

Other (OTH)

AF:

0.00

AC:

AN:

56906

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.012

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

PhyloP100

0.76

PrimateAI

Benign

0.42

PROVEAN

Benign

0.25

REVEL

Benign

0.16

Sift

Benign

0.072

Sift4G

Benign

0.60

Polyphen

0.0050

Vest4

0.18

MutPred

0.28

Gain of solvent accessibility (P = 0.0055)

MVP

0.21

MPC

0.37

ClinPred

0.17

GERP RS

4.2

Varity_R

0.059

gMVP

0.49

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over