chr17-2692579-G-C

Position:

• chr17-2692579-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366661.1(CLUH):​c.3430C>G​(p.Leu1144Val) 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 1,459,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLUH NM_001366661.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUH	NM_001366661.1	c.3430C>G	p.Leu1144Val	missense_variant	21/26	ENST00000651024.2	NP_001353590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUH	ENST00000651024.2	c.3430C>G	p.Leu1144Val	missense_variant	21/26		NM_001366661.1	ENSP00000498679.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459420 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726020

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.3313C>G (p.L1105V) alteration is located in exon 21 (coding exon 20) of the CLUH gene. This alteration results from a C to G substitution at nucleotide position 3313, causing the leucine (L) at amino acid position 1105 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T
Eigen	Benign	0.038
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;.;.
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.8	N;.;.
REVEL	Uncertain	0.51
Sift	Benign	0.099	T;.;.
Sift4G	Benign	0.26	T;T;.
Polyphen		0.64	P;P;.
Vest4		0.69
MutPred		0.65		Loss of stability (P = 0.2091);Loss of stability (P = 0.2091);.;
MVP		0.63
MPC		0.71
ClinPred		0.66	D
GERP RS		1.3
Varity_R		0.11
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-2595873;