Variant 5-124644634-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_020747.3(ZNF608):c.3733T>C(p.Tyr1245His) variant causes a missense change. The variant allele was found at a frequency of 0.00000424 in 1,416,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ZNF608
NM_020747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44

Variant links:

Genes affected

ZNF608 (HGNC:29238): (zinc finger protein 608) Predicted to enable metal ion binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF608 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38640258).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF608	NM_020747.3 link	c.3733T>C	p.Tyr1245His	missense_variant	6/10	ENST00000513986.2	NP_065798.2	Q9ULD9-1B3KPE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF608	ENST00000513986.2 link	c.3733T>C	p.Tyr1245His	missense_variant	6/10	2	NM_020747.3	ENSP00000421899.2		Q9ULD9-1B3KPE6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

223828

Hom.:

AF XY:

0.00000826

AC XY:

AN XY:

121002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000378

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000424

AC:

AN:

1416678

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000206

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:

0.0000171

GnomAD4 genome

Cov.:

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.3733T>C (p.Y1245H) alteration is located in exon 5 (coding exon 5) of the ZNF608 gene. This alteration results from a T to C substitution at nucleotide position 3733, causing the tyrosine (Y) at amino acid position 1245 to be replaced by a histidine (H). 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

Benign

0.30

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.1

.;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;D

Sift4G

Benign

0.49

T;T

Polyphen

0.89

.;P

Vest4

0.74

MutPred

0.24

.;Loss of sheet (P = 0.0315);

MVP

0.043

MPC

0.19

ClinPred

0.57

GERP RS

5.3

Varity_R

0.19

gMVP

0.19

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over