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GeneBe

19-53577934-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001079906.2(ZNF331):c.1374G>A(p.Gln458=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,612,760 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 14 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 12 hom. )

Consequence

ZNF331
NM_001079906.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.683
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 -15 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=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-53577934-G-A is Benign according to our data. Variant chr19-53577934-G-A is described in ClinVar as [Benign]. Clinvar id is 788474.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=0.683 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00521 (794/152336) while in subpopulation AFR AF= 0.0181 (751/41566). AF 95% confidence interval is 0.017. There are 14 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF331NM_001079906.2 linkuse as main transcriptc.1374G>A p.Gln458= synonymous_variant 6/6 ENST00000449416.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF331ENST00000449416.6 linkuse as main transcriptc.1374G>A p.Gln458= synonymous_variant 6/65 NM_001079906.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00520
AC:
791
AN:
152220
Hom.:
14
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00150
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00144
AC:
353
AN:
245894
Hom.:
8
AF XY:
0.00101
AC XY:
135
AN XY:
133300
show subpopulations
Gnomad AFR exome
AF:
0.0197
Gnomad AMR exome
AF:
0.000755
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000985
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000549
Gnomad OTH exome
AF:
0.000831
GnomAD4 exome
AF:
0.000578
AC:
844
AN:
1460424
Hom.:
12
Cov.:
34
AF XY:
0.000464
AC XY:
337
AN XY:
726330
show subpopulations
Gnomad4 AFR exome
AF:
0.0203
Gnomad4 AMR exome
AF:
0.000873
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00521
AC:
794
AN:
152336
Hom.:
14
Cov.:
33
AF XY:
0.00489
AC XY:
364
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0181
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00270
Hom.:
2
Bravo
AF:
0.00586
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

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
-0.79
Cadd
Benign
3.2
Dann
Benign
0.63

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: rs61741983; hg19: chr19-54081188; API