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GeneBe

7-149178673-A-T

Variant summary

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

The NM_170686.3(ZNF398):c.801A>T(p.Glu267Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZNF398
NM_170686.3 missense

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
Variant links:
Genes affected
ZNF398 (HGNC:18373): (zinc finger protein 398) This gene encodes a member of the Kruppel family of C2H2-type zinc-finger transcription factor proteins. The encoded protein acts as a transcriptional activator. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described, but their full length sequence has not been determined. [provided by RefSeq, Jul 2008]

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=0.15811813).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF398NM_170686.3 linkuse as main transcriptc.801A>T p.Glu267Asp missense_variant 6/6 ENST00000475153.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF398ENST00000475153.6 linkuse as main transcriptc.801A>T p.Glu267Asp missense_variant 6/61 NM_170686.3 P1Q8TD17-1
ZNF398ENST00000426851.6 linkuse as main transcriptc.288A>T p.Glu96Asp missense_variant 7/71 Q8TD17-2
ZNF398ENST00000483892.5 linkuse as main transcriptc.288A>T p.Glu96Asp missense_variant 6/65 Q8TD17-2
ZNF398ENST00000491174.1 linkuse as main transcriptc.288A>T p.Glu96Asp missense_variant 7/72 Q8TD17-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152204
Hom.:
0
Cov.:
32
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251104
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135728
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461514
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727072
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:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

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 GeneticsNov 29, 2021The c.801A>T (p.E267D) alteration is located in exon 6 (coding exon 6) of the ZNF398 gene. This alteration results from a A to T substitution at nucleotide position 801, causing the glutamic acid (E) at amino acid position 267 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
Benign
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
17
Dann
Uncertain
1.0
Eigen
Benign
0.069
Eigen_PC
Benign
0.090
FATHMM_MKL
Uncertain
0.86
D
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.92
N;N;N;N;N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.54
N;N;N;N
REVEL
Benign
0.047
Sift
Benign
0.22
T;T;T;T
Sift4G
Benign
0.14
T;T;T;T
Polyphen
0.91
.;P;.;.
Vest4
0.15
MVP
0.43
MPC
0.96
ClinPred
0.55
D
GERP RS
4.0
Varity_R
0.071
gMVP
0.33

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: rs776343314; hg19: chr7-148875765; API