Variant 17-2693905-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001366661.1(CLUH):c.3226G>A(p.Ala1076Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,611,094 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CLUH
NM_001366661.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044070452).

BS2

High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUH	NM_001366661.1 linkuse as main transcript	c.3226G>A	p.Ala1076Thr	missense_variant	19/26	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.3226G>A	p.Ala1076Thr	missense_variant	19/26		NM_001366661.1	ENSP00000498679.1		A0A494C0R8

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

240914

Hom.:

AF XY:

0.000145

AC XY:

AN XY:

131150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00152

Gnomad EAS exome

AF:

0.0000576

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000149

AC:

217

AN:

1458748

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

725484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000151

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.000132

AC:

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 22, 2023

The c.3109G>A (p.A1037T) alteration is located in exon 19 (coding exon 18) of the CLUH gene. This alteration results from a G to A substitution at nucleotide position 3109, causing the alanine (A) at amino acid position 1037 to be replaced by a threonine (T). 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

Benign

0.066

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

T;.;.

M_CAP

Benign

0.044

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.044

Sift

Benign

0.15

T;.;.

Sift4G

Benign

0.28

T;T;.

Polyphen

0.29

B;B;.

Vest4

0.29

MVP

0.41

MPC

0.32

ClinPred

0.050

GERP RS

3.3

Varity_R

0.027

gMVP

0.051

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