17-38731353-G-T

Variant names:

• chr17-38731353-G-T
• rs563305407
• NM_001136498.2:c.118G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136498.2(CISD3):​c.118G>T​(p.Val40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. V40M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CISD3 NM_001136498.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14058048).

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.118G>T	p.Val40Leu	missense	Exon 3 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.118G>T	p.Val40Leu	missense	Exon 3 of 4	ENSP00000483781.1	P0C7P0
	CISD3	ENST00000619858.1	TSL:1	n.471G>T		non_coding_transcript_exon	Exon 2 of 3
	CISD3	ENST00000894448.1		c.118G>T	p.Val40Leu	missense	Exon 3 of 4	ENSP00000564507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.4
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.093	T
Polyphen		0.11	B
Vest4		0.12
MutPred		0.42		Loss of sheet (P = 0.0037)
MVP		0.014
ClinPred		0.62	D
GERP RS		3.9
Varity_R		0.31
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs563305407; hg19: chr17-36887606;