chr3-126914744-C-T

Variant names:

• chr3-126914744-C-T
• rs776051047
• NM_032343.3:c.560C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032343.3(CHCHD6):​c.560C>T​(p.Thr187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,726 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. 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. T187K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHCHD6 NM_032343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07950738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD6	NM_032343.3	c.560C>T	p.Thr187Ile	missense_variant	Exon 6 of 8	ENST00000290913.8	NP_115719.1
CHCHD6	NM_001320610.2	c.563C>T	p.Thr188Ile	missense_variant	Exon 6 of 8		NP_001307539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD6	ENST00000290913.8	c.560C>T	p.Thr187Ile	missense_variant	Exon 6 of 8	1	NM_032343.3	ENSP00000290913.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251372 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1400726 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 700838

African (AFR) AF: 0.00 AC: 0 AN: 32280

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39398

South Asian (SAS) AF: 0.00 AC: 0 AN: 85066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056148

Other (OTH) AF: 0.00 AC: 0 AN: 58406

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.6
DANN	Benign	0.72
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.12
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.032
Sift	Benign	0.40	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.71	P;.
Vest4		0.14
MutPred		0.43		Loss of glycosylation at T187 (P = 0.0062);.;
MVP		0.19
MPC		0.25
ClinPred		0.29	T
GERP RS		0.23
Varity_R		0.069
gMVP		0.21
Mutation Taster		=95/5	polymorphism

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: rs776051047; hg19: chr3-126633587;