8-144829595-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000532777.6(ZNF7):​c.121G>T​(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,458,608 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ZNF7
ENST00000532777.6 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524
Variant links:
Genes affected
ZNF7 (HGNC:13139): (zinc finger protein 7) 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 integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF7NM_003416.4 linkuse as main transcriptc.121G>T p.Ala41Ser missense_variant 3/5 ENST00000532777.6 NP_003407.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF7ENST00000532777.6 linkuse as main transcriptc.121G>T p.Ala41Ser missense_variant 3/51 NM_003416.4 ENSP00000432641 P4P17097-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1458608
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
725092
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJan 06, 2023The c.121G>T (p.A41S) alteration is located in exon 3 (coding exon 2) of the ZNF7 gene. This alteration results from a G to T substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 to be replaced by a serine (S). 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
0.14
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T;.;.;T;.;T;T;T;T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.17
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.29
T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.0031
T
MetaRNN
Uncertain
0.48
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
.;.;L;.;.;.;.;L;.
MutationTaster
Benign
1.0
D;N;N;N;N;N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.9
N;N;N;N;N;N;N;N;D
REVEL
Benign
0.22
Sift
Benign
0.031
D;D;D;D;T;D;D;D;T
Sift4G
Benign
0.074
T;D;D;D;D;D;D;D;D
Polyphen
0.99, 0.99
.;.;.;.;.;.;.;D;D
Vest4
0.31, 0.24, 0.20, 0.13, 0.31, 0.18
MutPred
0.76
Gain of disorder (P = 0.0339);.;Gain of disorder (P = 0.0339);.;Gain of disorder (P = 0.0339);Gain of disorder (P = 0.0339);Gain of disorder (P = 0.0339);Gain of disorder (P = 0.0339);Gain of disorder (P = 0.0339);
MVP
0.52
MPC
0.40
ClinPred
0.82
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-146054980; API