7-132885667-C-T

Position:

• chr7-132885667-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000262570.10(CHCHD3):​c.448G>A​(p.Glu150Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHCHD3 ENST00000262570.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

Genes affected

CHCHD3 (HGNC:21906): (coiled-coil-helix-coiled-coil-helix domain containing 3) The protein encoded by this gene is an inner mitochondrial membrane scaffold protein. Absence of the encoded protein affects the structural integrity of mitochondrial cristae and leads to reductions in ATP production, cell growth, and oxygen consumption. This protein is part of the mitochondrial contact site and cristae organizing system (MICOS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21086171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHCHD3	NM_017812.4	c.448G>A	p.Glu150Lys	missense_variant	5/8	ENST00000262570.10	NP_060282.1
CHCHD3	NM_001317177.2	c.463G>A	p.Glu155Lys	missense_variant	6/9		NP_001304106.1
CHCHD3	XM_047420549.1	c.352G>A	p.Glu118Lys	missense_variant	5/8		XP_047276505.1
CHCHD3	NR_133671.2	n.691G>A		non_coding_transcript_exon_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHCHD3	ENST00000262570.10	c.448G>A	p.Glu150Lys	missense_variant	5/8	1	NM_017812.4	ENSP00000262570	A1
CHCHD3	ENST00000423635.5	c.538G>A	p.Glu180Lys	missense_variant, NMD_transcript_variant	6/11	1		ENSP00000410425
CHCHD3	ENST00000448878.6	c.463G>A	p.Glu155Lys	missense_variant	6/9	5		ENSP00000389297	P3
CHCHD3	ENST00000496427.5	n.358G>A		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 06, 2023

The c.448G>A (p.E150K) alteration is located in exon 5 (coding exon 5) of the CHCHD3 gene. This alteration results from a G to A substitution at nucleotide position 448, causing the glutamic acid (E) at amino acid position 150 to be replaced by a lysine (K). 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	0.21
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.13
Sift	Benign	0.29	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.054	B;B
Vest4		0.37
MutPred		0.50		.;Gain of MoRF binding (P = 7e-04);
MVP		0.43
MPC		0.26
ClinPred		0.76	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-132570427;