Genetic Variant CISD3:n.1978T>C (chr17-38734696-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000619858.1(CISD3):n.1978T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,478 control chromosomes in the GnomAD database, including 17,665 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.

Frequency

Genomes: 𝑓 0.48 ( 17579 hom., cov: 31)

Exomes 𝑓: 0.50 ( 86 hom. )

Consequence

CISD3
ENST00000619858.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.827

Publications

10 publications found

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:

PCGF2 (HGNC:12929): (polycomb group ring finger 2) The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses. [provided by RefSeq, Jul 2008]

PCGF2 Gene-Disease associations (from GenCC):

turnpenny-fry syndrome
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Broad Center for Mendelian Genomics, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

PCGF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCGF2	NM_007144.3 link	c.*527A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000620225.5	NP_009075.1	P35227A0A024R1V6
CISD3	NM_001136498.2 link	c.*1241T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000613478.2	NP_001129970.1	P0C7P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCGF2	ENST00000620225.5 link	c.*527A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_007144.3	ENSP00000482815.1		P35227
CISD3	ENST00000613478.2 link	c.*1241T>C		3_prime_UTR_variant	Exon 4 of 4	2	NM_001136498.2	ENSP00000483781.1		P0C7P0

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72562

AN:

151710

Hom.:

17555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.500

AC:

325

AN:

650

Hom.:

Cov.:

AF XY:

0.505

AC XY:

194

AN XY:

384

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.537

AC:

232

AN:

432

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.444

AC:

AN:

178

Other (OTH)

AF:

0.278

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.478

AC:

72630

AN:

151828

Hom.:

17579

Cov.:

AF XY:

0.480

AC XY:

35600

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.500

AC:

20693

AN:

41378

American (AMR)

AF:

0.422

AC:

6438

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1369

AN:

3468

East Asian (EAS)

AF:

0.281

AC:

1448

AN:

5160

South Asian (SAS)

AF:

0.479

AC:

2307

AN:

4816

European-Finnish (FIN)

AF:

0.572

AC:

6018

AN:

10514

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32787

AN:

67914

Other (OTH)

AF:

0.476

AC:

1006

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1936

3872

5808

7744

9680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.468

Hom.:

63056

Bravo

AF:

0.464

Asia WGS

AF:

0.431

AC:

1498

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.18

(source)

DANN

Benign

0.28

PhyloP100

-0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over