rs2879097

Variant names:

• chr17-38733306-C-T
• rs2879097
• NM_001136498.2:c.235C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001136498.2(CISD3):​c.235C>T​(p.Arg79Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,551,446 control chromosomes in the GnomAD database, including 39,210 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R79G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.18 (2889 hom., cov: 33)
  • Exomes 𝑓: 0.22 (36321 hom.)
• Consequence: CISD3 NM_001136498.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996
• Publications: 44 publications found

Genes affected

CISD3 (HGNC:27578): (CDGSH iron sulfur domain 3) CISD3 is a member of the CDGSH domain-containing family, which may play a role in regulating electron transport and oxidative phosphorylation (Wiley et al., 2007 [PubMed 17376863]).[supplied by OMIM, Apr 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136498.2. 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
	CISD3	NM_001136498.2	MANE Select	c.235C>T	p.Arg79Cys	missense	Exon 4 of 4	NP_001129970.1	P0C7P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CISD3	ENST00000613478.2	TSL:2 MANE Select	c.235C>T	p.Arg79Cys	missense	Exon 4 of 4	ENSP00000483781.1	P0C7P0
	CISD3	ENST00000619858.1	TSL:1	n.588C>T		non_coding_transcript_exon	Exon 3 of 3
	CISD3	ENST00000894448.1		c.295C>T	p.Arg99Cys	missense	Exon 4 of 4	ENSP00000564507.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27331 AN: 152136 Hom.: 2889 Cov.: 33

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.212 AC: 32679 AN: 153932 AF XY: 0.208

Gnomad AFR exome AF: 0.0653

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.223 AC: 312346 AN: 1399190 Hom.: 36321 Cov.: 36 AF XY: 0.222 AC XY: 153162 AN XY: 690118

African (AFR) AF: 0.0647 AC: 2045 AN: 31598

American (AMR) AF: 0.309 AC: 11040 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 5845 AN: 25176

East Asian (EAS) AF: 0.117 AC: 4178 AN: 35732

South Asian (SAS) AF: 0.168 AC: 13293 AN: 79222

European-Finnish (FIN) AF: 0.155 AC: 7616 AN: 49246

Middle Eastern (MID) AF: 0.191 AC: 1086 AN: 5698

European-Non Finnish (NFE) AF: 0.236 AC: 255108 AN: 1078832

Other (OTH) AF: 0.209 AC: 12135 AN: 58004

GnomAD4 genome AF: 0.180 AC: 27331 AN: 152256 Hom.: 2889 Cov.: 33 AF XY: 0.175 AC XY: 13058 AN XY: 74440

African (AFR) AF: 0.0695 AC: 2889 AN: 41556

American (AMR) AF: 0.270 AC: 4124 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3472

East Asian (EAS) AF: 0.138 AC: 715 AN: 5178

South Asian (SAS) AF: 0.164 AC: 790 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1547 AN: 10612

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15790 AN: 67994

Other (OTH) AF: 0.177 AC: 374 AN: 2112

Alfa AF: 0.214 Hom.: 11133

Bravo AF: 0.184

TwinsUK AF: 0.239 AC: 887

ALSPAC AF: 0.237 AC: 914

ExAC AF: 0.164 AC: 3963

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0062	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.71	D
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.0
PrimateAI	Benign	0.43	T
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.13
ClinPred		0.020	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: -30

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2879097; hg19: chr17-36889559;