chr12-133011394-C-T

Position:

• chr12-133011394-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_019591.4(ZNF26):​c.1515C>T​(p.Thr505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,611,016 control chromosomes in the GnomAD database, including 370,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34596 hom., cov: 33)
  • Exomes 𝑓: 0.68 (335675 hom.)
• Consequence: ZNF26 NM_019591.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.83

Genes affected

ZNF26 (HGNC:13053): (zinc finger protein 26) Predicted to enable DNA-binding transcription factor 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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 12-133011394-C-T is Benign according to our data. Variant chr12-133011394-C-T is described in ClinVar as [Benign]. Clinvar id is 982073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF26	NM_019591.4	c.1515C>T	p.Thr505=	synonymous_variant	4/4	ENST00000328654.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF26	ENST00000328654.10	c.1515C>T	p.Thr505=	synonymous_variant	4/4	1	NM_019591.4	P1
ZNF26	ENST00000534834.1	n.4120C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102057 AN: 151928 Hom.: 34587 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.717

GnomAD4 exome AF: 0.675 AC: 985473 AN: 1458972 Hom.: 335675 Cov.: 46 AF XY: 0.678 AC XY: 491655 AN XY: 725452

Gnomad4 AFR exome AF: 0.593

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.852

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.693

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.689

GnomAD4 genome AF: 0.672 AC: 102101 AN: 152044 Hom.: 34596 Cov.: 33 AF XY: 0.678 AC XY: 50347 AN XY: 74294

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.719

Alfa AF: 0.629 Hom.: 6676

Bravo AF: 0.676

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Pathology and Clinical Laboratory Medicine, King Fahad Medical City

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.46
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs3825108; hg19: chr12-133587980;