dbSNP rs535247574: CISD3:p.Arg16Gln (chr17-38730405-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136498.2(CISD3):c.47G>A(p.Arg16Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CISD3
NM_001136498.2 missense, splice_region

Scores

Splicing: ADA: 0.001384

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.868

Variant links:

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]

CISD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 (MetaRNN=0.06679121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CISD3	NM_001136498.2 link	c.47G>A	p.Arg16Gln	missense_variant, splice_region_variant	Exon 1 of 4	ENST00000613478.2	NP_001129970.1	P0C7P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CISD3	ENST00000613478.2 link	c.47G>A	p.Arg16Gln	missense_variant, splice_region_variant	Exon 1 of 4	2	NM_001136498.2	ENSP00000483781.1		P0C7P0
CISD3	ENST00000619858.1 link	n.47G>A		non_coding_transcript_exon_variant	Exon 1 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1066672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

504474

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151072

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73762

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.00052

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.21

M_CAP

Benign

0.0056

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.46

Sift4G

Benign

0.29

Polyphen

0.029

Vest4

0.085

MutPred

0.22

Loss of MoRF binding (P = 0.0502);

MVP

0.014

ClinPred

0.076

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.13

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over