rs1035293

Variant names:

• chr7-132999547-G-A
• rs1035293
• NM_017812.4:c.252-24261C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017812.4(CHCHD3):​c.252-24261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,828 control chromosomes in the GnomAD database, including 15,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15322 hom., cov: 33)
• Consequence: CHCHD3 NM_017812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD3	NM_017812.4	c.252-24261C>T		intron_variant	Intron 3 of 7	ENST00000262570.10	NP_060282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD3	ENST00000262570.10	c.252-24261C>T		intron_variant	Intron 3 of 7	1	NM_017812.4	ENSP00000262570.5

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67590 AN: 151706 Hom.: 15311 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.470

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67624 AN: 151828 Hom.: 15322 Cov.: 33 AF XY: 0.446 AC XY: 33100 AN XY: 74196

African (AFR) AF: 0.415 AC: 17215 AN: 41446

American (AMR) AF: 0.505 AC: 7691 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3464

East Asian (EAS) AF: 0.546 AC: 2819 AN: 5162

South Asian (SAS) AF: 0.360 AC: 1731 AN: 4802

European-Finnish (FIN) AF: 0.419 AC: 4406 AN: 10518

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30308 AN: 67892

Other (OTH) AF: 0.471 AC: 990 AN: 2100

Alfa AF: 0.447 Hom.: 2557

Bravo AF: 0.452

Asia WGS AF: 0.442 AC: 1527 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.41
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs1035293; hg19: chr7-132684307;