19-12145469-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145233.4(ZNF625):​c.947C>G​(p.Ser316Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. S316L) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)

Consequence

ZNF625
NM_145233.4 missense

Scores

1
3
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.211
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-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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23735595).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF625NM_145233.4 linkc.947C>G p.Ser316Trp missense_variant Exon 4 of 4 ENST00000439556.3 NP_660276.2 Q96I27-2
ZNF625NR_037801.2 linkn.1119C>G non_coding_transcript_exon_variant Exon 4 of 4
ZNF625-ZNF20NR_037802.1 linkn.364+1926C>G intron_variant Intron 3 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF625ENST00000439556.3 linkc.947C>G p.Ser316Trp missense_variant Exon 4 of 4 2 NM_145233.4 ENSP00000394380.2 Q96I27-2
ZNF625-ZNF20ENST00000430024.5 linkn.191+1926C>G intron_variant Intron 3 of 7 5 ENSP00000457423.1 F8WDT6

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151804
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251458
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
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
Cov.:
29
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151804
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74112
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
17
DANN
Uncertain
0.99
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Benign
0.053
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0040
D
Vest4
0.32
MVP
0.28
MPC
1.7
ClinPred
0.98
D
GERP RS
-0.40
gMVP
0.022

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.

Other links and lift over

dbSNP: rs778993312; hg19: chr19-12256284; API