Variant 3-126704374-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032343.3(CHCHD6):c.62G>T(p.Arg21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 1,422,904 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CHCHD6
NM_032343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

CHCHD6 (HGNC:28184): (coiled-coil-helix-coiled-coil-helix domain containing 6) Involved in cellular response to DNA damage stimulus and cristae formation. Located in cytosol and mitochondrial inner membrane. Part of MICOS complex. [provided by Alliance of Genome Resources, Apr 2022]

CHCHD6 links:

CHCHD6 (HGNC:):

CHCHD6 links:

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ACMG classification

Classification made for transcript

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
CHCHD6	NM_032343.3 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/8	ENST00000290913.8	NP_115719.1	Q9BRQ6
CHCHD6	NM_001320610.2 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/8		NP_001307539.1	Q9BRQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHCHD6	ENST00000290913.8 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/8	1	NM_032343.3	ENSP00000290913.3	Q9BRQ6
CHCHD6	ENST00000508789.5 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	1/7	1		ENSP00000422912.1	J3QTA6
CHCHD6	ENST00000503119.5 linkuse as main transcript	n.62G>T		non_coding_transcript_exon_variant	1/8	1		ENSP00000427517.1	J3QTB2
CHCHD6	ENST00000514908.5 linkuse as main transcript	n.132G>T		non_coding_transcript_exon_variant	1/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000422

AC:

AN:

1422904

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

704880

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:

0.0000733

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000849

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

Sep 30, 2024

The c.62G>T (p.R21L) alteration is located in exon 1 (coding exon 1) of the CHCHD6 gene. This alteration results from a G to T substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a leucine (L). 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

Uncertain

0.49

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;T

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.63

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;.

Vest4

0.75

MutPred

0.53

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.62

MPC

0.37

ClinPred

0.97

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.66

gMVP

0.35

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