rs113889670

Variant names:

• chr22-23765954-G-A
• rs113889670
• NM_213720.3:c.*53C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_213720.3(CHCHD10):​c.*53C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,612,428 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (18 hom.)
• Consequence: CHCHD10 NM_213720.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.181
• Publications: 1 publications found

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]

C22orf15 (HGNC:15558): (chromosome 22 open reading frame 15)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-23765954-G-A is Benign according to our data. Variant chr22-23765954-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1200484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0066 (1004/152216) while in subpopulation AFR AF = 0.0232 (964/41530). AF 95% confidence interval is 0.022. There are 10 homozygotes in GnomAd4. There are 498 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1004 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213720.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHCHD10	NM_213720.3	MANE Select	c.*53C>T		3_prime_UTR	Exon 4 of 4	NP_998885.1	Q8WYQ3
	CHCHD10	NM_001301339.2		c.*53C>T		3_prime_UTR	Exon 4 of 4	NP_001288268.1	B5MBW9
	CHCHD10	NR_125755.2		n.527C>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHCHD10	ENST00000484558.3	TSL:1 MANE Select	c.*53C>T		3_prime_UTR	Exon 4 of 4	ENSP00000418428.3	Q8WYQ3
	CHCHD10	ENST00000878118.1		c.*53C>T		3_prime_UTR	Exon 4 of 4	ENSP00000548177.1
	CHCHD10	ENST00000878120.1		c.*53C>T		3_prime_UTR	Exon 4 of 4	ENSP00000548179.1

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 993 AN: 152098 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.000736 AC: 1075 AN: 1460212 Hom.: 18 Cov.: 32 AF XY: 0.000626 AC XY: 455 AN XY: 726400

African (AFR) AF: 0.0244 AC: 818 AN: 33458

American (AMR) AF: 0.00128 AC: 57 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00116 AC: 6 AN: 5166

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111436

Other (OTH) AF: 0.00239 AC: 144 AN: 60266

GnomAD4 genome AF: 0.00660 AC: 1004 AN: 152216 Hom.: 10 Cov.: 33 AF XY: 0.00669 AC XY: 498 AN XY: 74424

African (AFR) AF: 0.0232 AC: 964 AN: 41530

American (AMR) AF: 0.00163 AC: 25 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67994

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.0143 Hom.: 4

Bravo AF: 0.00813

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs113889670; hg19: chr22-24108141;