chr19-53577504-C-T

Variant summary

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

The NM_001079906.2(ZNF331):​c.944C>T​(p.Thr315Ile) 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 1,612,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90
Variant links:
Genes affected
ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

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=0.24050218).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF331NM_001079906.2 linkuse as main transcriptc.944C>T p.Thr315Ile missense_variant 6/6 ENST00000449416.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF331ENST00000449416.6 linkuse as main transcriptc.944C>T p.Thr315Ile missense_variant 6/65 NM_001079906.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152070
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00000795
AC:
2
AN:
251472
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135922
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460582
Hom.:
0
Cov.:
34
AF XY:
0.0000138
AC XY:
10
AN XY:
726648
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
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:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152070
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.0000383
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

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 GeneticsFeb 21, 2024The c.944C>T (p.T315I) alteration is located in exon 7 (coding exon 3) of the ZNF331 gene. This alteration results from a C to T substitution at nucleotide position 944, causing the threonine (T) at amino acid position 315 to be replaced by an isoleucine (I). 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
0.16
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T;T;T;T;T;T;T;T;T;T;T;T
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.48
.;.;.;.;T;.;.;.;.;.;.;.;.
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.24
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.25
N;N;N;N;N;N;N;N;N;N;N;N;N
MutationTaster
Benign
1.0
D;N;N;N;N;N;N;N
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.3
.;D;.;D;D;D;D;.;D;D;.;.;.
REVEL
Benign
0.17
Sift
Benign
0.27
.;T;.;T;T;T;T;.;T;T;.;.;.
Sift4G
Benign
0.35
.;T;.;T;T;T;T;.;T;T;.;.;.
Polyphen
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D
Vest4
0.10, 0.11, 0.14, 0.12, 0.13
MVP
0.36
MPC
1.7
ClinPred
0.74
D
GERP RS
3.9
Varity_R
0.21
gMVP
0.10

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: rs148784378; hg19: chr19-54080758; API