chr22-23767827-C-G

Variant names:

• chr22-23767827-C-G
• NM_213720.3:c.41+7G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_213720.3(CHCHD10):​c.41+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CHCHD10 NM_213720.3 splice_region, intron
• Scores: Splicing: ADA: 0.00008758
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

CHCHD10 (HGNC:15559): (coiled-coil-helix-coiled-coil-helix domain containing 10) This gene encodes a mitochondrial protein that is enriched at cristae junctions in the intermembrane space. It may play a role in cristae morphology maintenance or oxidative phosphorylation. Mutations in this gene cause frontotemporal dementia and/or amyotrophic lateral sclerosis-2. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 7 and 19. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD10	NM_213720.3	c.41+7G>C		splice_region_variant, intron_variant	Intron 1 of 3	ENST00000484558.3	NP_998885.1
CHCHD10	NM_001301339.2	c.41+7G>C		splice_region_variant, intron_variant	Intron 1 of 3		NP_001288268.1
CHCHD10	NR_125755.2	n.139+7G>C		splice_region_variant, intron_variant	Intron 1 of 3
CHCHD10	NR_125756.2	n.139+7G>C		splice_region_variant, intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD10	ENST00000484558.3	c.41+7G>C		splice_region_variant, intron_variant	Intron 1 of 3	1	NM_213720.3	ENSP00000418428.3
CHCHD10	ENST00000401675.7	c.41+7G>C		splice_region_variant, intron_variant	Intron 1 of 3	5		ENSP00000384973.3
CHCHD10	ENST00000520222.1	c.41+7G>C		splice_region_variant, intron_variant	Intron 1 of 2	3		ENSP00000430042.1
CHCHD10	ENST00000517886.1	n.41+7G>C		splice_region_variant, intron_variant	Intron 1 of 3	3		ENSP00000429976.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389598 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 688550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.57
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000088
dbscSNV1_RF	Benign	0.0040
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: chr22-24110014;