Genetic Variant ZNF625:p.Asp49Tyr (chr19-12147441-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145233.4(ZNF625):c.145G>T(p.Asp49Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000993 in 1,532,168 control chromosomes in the GnomAD database, including 17 homozygotes. 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. D49N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 15 hom. )

Consequence

ZNF625
NM_145233.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0670

Publications

4 publications found

Variant links:

Genes affected

ZNF625 (HGNC:30571): (zinc finger protein 625) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF625 links:

ZNF625-ZNF20 (HGNC:48368): (ZNF625-ZNF20 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 625 (ZNF625) and zinc finger protein 20 (ZNF20) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ZNF625-ZNF20 links:

ENSG00000290812 (HGNC:):

ENSG00000290812 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043751597).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145233.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF625	NM_145233.4	MANE Select	c.145G>T	p.Asp49Tyr	missense	Exon 3 of 4	NP_660276.2	Q96I27-2
ZNF625	NR_037801.2		n.317G>T		non_coding_transcript_exon	Exon 3 of 4
ZNF625-ZNF20	NR_037802.1		n.318G>T		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF625	ENST00000439556.3	TSL:2 MANE Select	c.145G>T	p.Asp49Tyr	missense	Exon 3 of 4	ENSP00000394380.2	Q96I27-2
ZNF625	ENST00000455799.1	TSL:1	c.141G>T	p.Lys47Asn	missense	Exon 3 of 4	ENSP00000398518.1	F2Z3I2
ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.145G>T		non_coding_transcript_exon	Exon 3 of 8	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes

AF:

0.000999

AC:

152

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00278

AC:

386

AN:

138946

AF XY:

0.00320

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.000144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.0000920

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.000992

AC:

1369

AN:

1379888

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

847

AN XY:

680448

show subpopulations

African (AFR)

AF:

0.000618

AC:

AN:

30764

American (AMR)

AF:

0.000220

AC:

AN:

31836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24830

East Asian (EAS)

AF:

0.00768

AC:

274

AN:

35676

South Asian (SAS)

AF:

0.00921

AC:

700

AN:

76022

European-Finnish (FIN)

AF:

0.0000244

AC:

AN:

40946

Middle Eastern (MID)

AF:

0.000532

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.000160

AC:

172

AN:

1076592

Other (OTH)

AF:

0.00335

AC:

193

AN:

57586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00100

AC:

153

AN:

152280

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41552

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0133

AC:

AN:

5188

South Asian (SAS)

AF:

0.0120

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68026

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000466

Hom.:

Bravo

AF:

0.000722

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00175

AC:

111

Asia WGS

AF:

0.0380

AC:

132

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.91

PhyloP100

0.067

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-7.2

REVEL

Benign

0.035

Sift

Benign

0.030

Sift4G

Pathogenic

0.0

Vest4

0.19

MVP

0.18

MPC

0.94

ClinPred

0.11

GERP RS

0.47

PromoterAI

-0.0049

Neutral

(source)

gMVP

0.048

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over