2-112586089-A-G

Position:

• chr2-112586089-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032309.4(CHCHD5):​c.118A>G​(p.Ser40Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHCHD5 NM_032309.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62

Genes affected

CHCHD5 (HGNC:17840): (coiled-coil-helix-coiled-coil-helix domain containing 5) Predicted to be located in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27027935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHCHD5	NM_032309.4	c.118A>G	p.Ser40Gly	missense_variant	2/4	ENST00000324913.10	NP_115685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHCHD5	ENST00000324913.10	c.118A>G	p.Ser40Gly	missense_variant	2/4	1	NM_032309.4	ENSP00000325655	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

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

Sep 20, 2023

The c.118A>G (p.S40G) alteration is located in exon 2 (coding exon 2) of the CHCHD5 gene. This alteration results from a A to G substitution at nucleotide position 118, causing the serine (S) at amino acid position 40 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T;.
Eigen	Benign	0.0015
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	0.82	D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.075
Sift	Benign	0.050	D;D
Polyphen		0.23	B;.
Vest4		0.50
MutPred		0.32		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.30
MPC		0.019
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.084
gMVP		0.50

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: chr2-113343666;