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16-31061887-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_024706.5(ZNF668):c.1041G>A(p.Ala347=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,612,962 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00098 ( 18 hom. )

Consequence

ZNF668
NM_024706.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.74
Variant links:
Genes affected
ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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 16-31061887-C-T is Benign according to our data. Variant chr16-31061887-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043623.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=-2.74 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000983 (1436/1460608) while in subpopulation EAS AF= 0.022 (873/39676). AF 95% confidence interval is 0.0208. There are 18 homozygotes in gnomad4_exome. There are 711 alleles in male gnomad4_exome subpopulation. Median coverage is 31. 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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF668NM_024706.5 linkuse as main transcriptc.1041G>A p.Ala347= synonymous_variant 3/3 ENST00000300849.5
ZNF668NM_001172669.2 linkuse as main transcriptc.1110G>A p.Ala370= synonymous_variant 4/4
ZNF668NM_001172668.2 linkuse as main transcriptc.1041G>A p.Ala347= synonymous_variant 3/3
ZNF668NM_001172670.2 linkuse as main transcriptc.1041G>A p.Ala347= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF668ENST00000300849.5 linkuse as main transcriptc.1041G>A p.Ala347= synonymous_variant 3/31 NM_024706.5 P1
ENST00000622229.1 linkuse as main transcriptn.2464C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00145
AC:
220
AN:
152236
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00818
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0114
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00155
AC:
385
AN:
248012
Hom.:
3
AF XY:
0.00137
AC XY:
185
AN XY:
134768
show subpopulations
Gnomad AFR exome
AF:
0.000506
Gnomad AMR exome
AF:
0.00621
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00720
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000179
Gnomad OTH exome
AF:
0.00198
GnomAD4 exome
AF:
0.000983
AC:
1436
AN:
1460608
Hom.:
18
Cov.:
31
AF XY:
0.000979
AC XY:
711
AN XY:
726574
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.00757
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0220
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000117
Gnomad4 OTH exome
AF:
0.00126
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00144
AC:
220
AN:
152354
Hom.:
1
Cov.:
32
AF XY:
0.00160
AC XY:
119
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.00817
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0114
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000335
Hom.:
0
Bravo
AF:
0.00149
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

ZNF668-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 08, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
6.6
Dann
Benign
0.88

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: rs2288003; hg19: chr16-31073208; API