Variant 2-112586099-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032309.4(CHCHD5):c.128A>G(p.Gln43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,571,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

CHCHD5
NM_032309.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.72

Variant links:

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]

CHCHD5 links:

CHCHD5 (HGNC:):

CHCHD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054465115).

BP6

Variant 2-112586099-A-G is Benign according to our data. Variant chr2-112586099-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3144069.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHCHD5	NM_032309.4 linkuse as main transcript	c.128A>G	p.Gln43Arg	missense_variant	2/4	ENST00000324913.10	NP_115685.1	Q9BSY4-1A0A2U9EWT9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHCHD5	ENST00000324913.10 linkuse as main transcript	c.128A>G	p.Gln43Arg	missense_variant	2/4	1	NM_032309.4	ENSP00000325655.5		Q9BSY4-1

Frequencies

GnomAD3 genomes

AF:

0.0000949

AC:

AN:

147502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251330

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000772

AC:

AN:

1424052

Hom.:

Cov.:

AF XY:

0.00000707

AC XY:

AN XY:

707620

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000948

AC:

AN:

147634

Hom.:

Cov.:

AF XY:

0.0000555

AC XY:

AN XY:

72088

show subpopulations

Gnomad4 AFR

AF:

0.000318

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.7

DANN

Benign

0.87

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.075

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.012

Sift

Benign

0.59

T;T

Polyphen

0.0

B;.

Vest4

0.26

MutPred

0.21

Gain of MoRF binding (P = 0.0127);Gain of MoRF binding (P = 0.0127);

MVP

0.21

MPC

0.018

ClinPred

0.0051

GERP RS

0.73

Varity_R

0.033

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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