Genetic Variant NM_183238.4:c.*2478G>A (chr12-132922895-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_183238.4(ZNF605):c.*2478G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,040 control chromosomes in the GnomAD database, including 14,635 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 0.43 ( 14632 hom., cov: 32)

Exomes 𝑓: 0.35 ( 3 hom. )

Consequence

ZNF605
NM_183238.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.303

Publications

18 publications found

Variant links:

Genes affected

ZNF605 (HGNC:28068): (zinc finger protein 605) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF605 links:

CHFR (HGNC:20455): (checkpoint with forkhead and ring finger domains) This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]

CHFR links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF605	NM_183238.4 link	c.*2478G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000360187.9	NP_899061.1	Q86T29-1
ZNF605	NM_001164715.2 link	c.*2478G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001158187.1	Q86T29-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF605	ENST00000360187.9 link	c.*2478G>A	3_prime_UTR_variant	Exon 5 of 5	1	NM_183238.4	ENSP00000353314.3	Q86T29-1
ZNF605	ENST00000392321.3 link	c.*2478G>A	3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000376135.3	Q86T29-2
CHFR	ENST00000536932.5 link	c.-252+22726G>A	intron_variant	Intron 2 of 5	4		ENSP00000475247.1	U3KPU9

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65176

AN:

151896

Hom.:

14625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.346

AC:

AN:

Hom.:

Cov.:

AF XY:

0.350

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.300

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.429

AC:

65202

AN:

152014

Hom.:

14632

Cov.:

AF XY:

0.425

AC XY:

31563

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.343

AC:

14206

AN:

41452

American (AMR)

AF:

0.446

AC:

6807

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

1871

AN:

3464

East Asian (EAS)

AF:

0.218

AC:

1126

AN:

5172

South Asian (SAS)

AF:

0.528

AC:

2541

AN:

4812

European-Finnish (FIN)

AF:

0.358

AC:

3791

AN:

10578

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33163

AN:

67954

Other (OTH)

AF:

0.481

AC:

1012

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1884

3769

5653

7538

9422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.470

Hom.:

48714

Bravo

AF:

0.430

Asia WGS

AF:

0.398

AC:

1386

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.3

(source)

DANN

Benign

0.70

PhyloP100

0.30

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over