16-30525202-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024671.4(ZNF768):​c.938G>A​(p.Gly313Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,450 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: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF768
NM_024671.4 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.940
Variant links:
Genes affected
ZNF768 (HGNC:26273): (zinc finger protein 768) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33361012).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF768NM_024671.4 linkc.938G>A p.Gly313Asp missense_variant Exon 2 of 2 ENST00000380412.7 NP_078947.3 Q9H5H4A0A024QZC8
ZNF768XM_017023665.3 linkc.1010G>A p.Gly337Asp missense_variant Exon 2 of 2 XP_016879154.1
ZNF768XM_017023666.2 linkc.845G>A p.Gly282Asp missense_variant Exon 2 of 2 XP_016879155.1 H3BS42

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF768ENST00000380412.7 linkc.938G>A p.Gly313Asp missense_variant Exon 2 of 2 1 NM_024671.4 ENSP00000369777.5 Q9H5H4
ZNF768ENST00000562803.1 linkc.845G>A p.Gly282Asp missense_variant Exon 2 of 2 3 ENSP00000456527.1 H3BS42

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151596
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461854
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727234
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151596
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74012
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.938G>A (p.G313D) alteration is located in exon 2 (coding exon 2) of the ZNF768 gene. This alteration results from a G to A substitution at nucleotide position 938, causing the glycine (G) at amino acid position 313 to be replaced by an aspartic acid (D). 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
Pathogenic
0.99
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.3
L;.
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-6.4
D;.
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.38
MutPred
0.44
Gain of solvent accessibility (P = 0.039);.;
MVP
0.35
MPC
2.0
ClinPred
0.99
D
GERP RS
4.7
Varity_R
0.75
gMVP
0.75

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: rs1326977832; hg19: chr16-30536523; COSMIC: COSV63323358; COSMIC: COSV63323358; API