Variant chr17-2692036-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001366661.1(CLUH):c.3622G>C(p.Glu1208Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,443,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000042 ( 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: 7.87

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:

CLUH (HGNC:):

CLUH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUH	NM_001366661.1 linkuse as main transcript	c.3622G>C	p.Glu1208Gln	missense_variant	23/26	ENST00000651024.2	NP_001353590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUH	ENST00000651024.2 linkuse as main transcript	c.3622G>C	p.Glu1208Gln	missense_variant	23/26		NM_001366661.1	ENSP00000498679.1		A0A494C0R8

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1443050

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

717332

show subpopulations

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:

0.00000454

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000665

AC:

AN:

150288

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73278

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.3505G>C (p.E1169Q) alteration is located in exon 23 (coding exon 22) of the CLUH gene. This alteration results from a G to C substitution at nucleotide position 3505, causing the glutamic acid (E) at amino acid position 1169 to be replaced by a glutamine (Q). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D;D

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;.;.

M_CAP

Pathogenic

0.44

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Pathogenic

0.95

MutationAssessor

Uncertain

2.7

M;M;.

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.4

N;.;.

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.0050

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.78

MutPred

0.44

Gain of MoRF binding (P = 0.0513);Gain of MoRF binding (P = 0.0513);.;

MVP

0.86

MPC

1.0

ClinPred

0.98

GERP RS

4.8

Varity_R

0.63

gMVP

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over