Genetic Variant CLUH:p.Glu1137Asp (chr17-2692598-T-G) – 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.3411A>C(p.Glu1137Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,322 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLUH
NM_001366661.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.186

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:

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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=0.2513027).

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.3411A>C	p.Glu1137Asp	missense	Exon 21 of 26	NP_001353590.1	A0A494C0R8
CLUH	NM_015229.4		c.3408A>C	p.Glu1136Asp	missense	Exon 21 of 26	NP_056044.4
CLUH	NM_001366662.1		c.3294A>C	p.Glu1098Asp	missense	Exon 21 of 26	NP_001353591.1	O75153

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLUH	ENST00000651024.2	MANE Select	c.3411A>C	p.Glu1137Asp	missense	Exon 21 of 26	ENSP00000498679.1	A0A494C0R8
CLUH	ENST00000574210.5	TSL:1	n.735A>C		non_coding_transcript_exon	Exon 5 of 9
CLUH	ENST00000876318.1		c.3429A>C	p.Glu1143Asp	missense	Exon 21 of 26	ENSP00000546377.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460322

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111552

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.060

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.6

PhyloP100

-0.19

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.31

Sift

Benign

0.093

Sift4G

Benign

0.092

Polyphen

0.26

Vest4

0.41

MutPred

0.37

Loss of disorder (P = 0.3765)

MVP

0.52

MPC

0.36

ClinPred

0.55

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.46

Mutation Taster

=73/27

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

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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