Genetic Variant ZNF625:p.Val290Phe (chr19-12145548-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145233.4(ZNF625):c.868G>T(p.Val290Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. V290I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF625
NM_145233.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.49

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046981007).

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.868G>T	p.Val290Phe	missense	Exon 4 of 4	NP_660276.2	Q96I27-2
ZNF625	NR_037801.2		n.1040G>T		non_coding_transcript_exon	Exon 4 of 4
ZNF625-ZNF20	NR_037802.1		n.364+1847G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF625	ENST00000439556.3	TSL:2 MANE Select	c.868G>T	p.Val290Phe	missense	Exon 4 of 4	ENSP00000394380.2	Q96I27-2
ZNF625	ENST00000455799.1	TSL:1	c.*678G>T		3_prime_UTR	Exon 4 of 4	ENSP00000398518.1	F2Z3I2
ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.191+1847G>T		intron	N/A	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455568

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

85992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106394

Other (OTH)

AF:

0.00

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.23

(source)

DANN

Uncertain

0.98

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.014

M_CAP

Benign

0.0012

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.99

PhyloP100

-6.5

PrimateAI

Benign

0.32

PROVEAN

Benign

0.75

REVEL

Benign

0.029

Sift

Benign

0.59

Sift4G

Benign

0.53

Vest4

0.096

MVP

0.055

MPC

0.66

ClinPred

0.059

GERP RS

-1.7

gMVP

0.054

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over