chr3-126704374-G-C

Variant names:

• chr3-126704374-G-C
• rs748360128
• NM_032343.3:c.62G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032343.3(CHCHD6):​c.62G>C​(p.Arg21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHCHD6 NM_032343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 0 publications found

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]

ENSG00000308864 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD6	NM_032343.3	c.62G>C	p.Arg21Pro	missense_variant	Exon 1 of 8	ENST00000290913.8	NP_115719.1
CHCHD6	NM_001320610.2	c.62G>C	p.Arg21Pro	missense_variant	Exon 1 of 8		NP_001307539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD6	ENST00000290913.8	c.62G>C	p.Arg21Pro	missense_variant	Exon 1 of 8	1	NM_032343.3	ENSP00000290913.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.62	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.49		Loss of MoRF binding (P = 0.0146);Loss of MoRF binding (P = 0.0146);
MVP		0.45
MPC		0.40
ClinPred		0.99	D
GERP RS		3.9
PromoterAI		-0.0023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.87
gMVP		0.45
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs748360128; hg19: chr3-126423217;