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GeneBe

19-53571727-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001079906.2(ZNF331):c.133C>T(p.Leu45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,610,354 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 101 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 101 hom. )

Consequence

ZNF331
NM_001079906.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.244
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-53571727-C-T is Benign according to our data. Variant chr19-53571727-C-T is described in ClinVar as [Benign]. Clinvar id is 779045.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.244 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF331NM_001079906.2 linkuse as main transcriptc.133C>T p.Leu45= synonymous_variant 5/6 ENST00000449416.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF331ENST00000449416.6 linkuse as main transcriptc.133C>T p.Leu45= synonymous_variant 5/65 NM_001079906.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0195
AC:
2973
AN:
152178
Hom.:
100
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0668
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00937
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.0167
GnomAD3 exomes
AF:
0.00536
AC:
1326
AN:
247396
Hom.:
51
AF XY:
0.00395
AC XY:
529
AN XY:
133830
show subpopulations
Gnomad AFR exome
AF:
0.0694
Gnomad AMR exome
AF:
0.00461
Gnomad ASJ exome
AF:
0.000102
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000133
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000233
Gnomad OTH exome
AF:
0.00199
GnomAD4 exome
AF:
0.00211
AC:
3077
AN:
1458058
Hom.:
101
Cov.:
31
AF XY:
0.00188
AC XY:
1365
AN XY:
725146
show subpopulations
Gnomad4 AFR exome
AF:
0.0696
Gnomad4 AMR exome
AF:
0.00539
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000221
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.00538
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0196
AC:
2983
AN:
152296
Hom.:
101
Cov.:
32
AF XY:
0.0189
AC XY:
1407
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0668
Gnomad4 AMR
AF:
0.00936
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.00580
Hom.:
9
Bravo
AF:
0.0230
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000328
EpiControl
AF:
0.000415

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
6.1
Dann
Benign
0.77

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: rs61741794; hg19: chr19-54074981; API