17-38733321-C-T

Variant names:

• chr17-38733321-C-T
• NM_001136498.2:c.250C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136498.2(CISD3):​c.250C>T​(p.Pro84Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CISD3 NM_001136498.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CISD3	NM_001136498.2	c.250C>T	p.Pro84Ser	missense_variant	Exon 4 of 4	ENST00000613478.2	NP_001129970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CISD3	ENST00000613478.2	c.250C>T	p.Pro84Ser	missense_variant	Exon 4 of 4	2	NM_001136498.2	ENSP00000483781.1
CISD3	ENST00000619858.1	n.603C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
CISD3	ENST00000616128.1	n.379C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250C>T (p.P84S) alteration is located in exon 4 (coding exon 4) of the CISD3 gene. This alteration results from a C to T substitution at nucleotide position 250, causing the proline (P) at amino acid position 84 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.048	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.54	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.81		Loss of methylation at K86 (P = 0.0526);
MVP		0.067
ClinPred		0.98	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-36889574;