rs35575803

Variant names:

• chr19-20624371-G-GA
• rs35575803
• NM_001076675.3:c.1505dupT

Your query was ambiguous. Multiple possible variants found:

• chr19-20624371-G-GA
• chr19-20624371-G-GAAATTGTAGAATTTCTCTCCAGTATGA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001076675.3(ZNF626):​c.1505dupT​(p.Ile503HisfsTer95) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (42309 hom., cov: 0)
  • Exomes 𝑓: 0.72 (197533 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 10 publications found

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269110 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 42309 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076675.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	NM_001076675.3	MANE Select	c.1505dupT	p.Ile503HisfsTer95	frameshift	Exon 4 of 4	NP_001070143.1	Q68DY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	ENST00000601440.6	TSL:4 MANE Select	c.1505dupT	p.Ile503HisfsTer95	frameshift	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+21312dupT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.778 AC: 106329 AN: 136752 Hom.: 42310 Cov.: 0

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.812

GnomAD2 exomes AF: 0.429 AC: 33280 AN: 77600 AF XY: 0.426

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.354

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.422

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.723 AC: 487876 AN: 674986 Hom.: 197533 Cov.: 27 AF XY: 0.720 AC XY: 243796 AN XY: 338590

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.448 AC: 10443 AN: 23314

American (AMR) AF: 0.670 AC: 12826 AN: 19144

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 10400 AN: 14136

East Asian (EAS) AF: 0.735 AC: 19430 AN: 26424

South Asian (SAS) AF: 0.645 AC: 31049 AN: 48116

European-Finnish (FIN) AF: 0.771 AC: 28928 AN: 37496

Middle Eastern (MID) AF: 0.723 AC: 2008 AN: 2778

European-Non Finnish (NFE) AF: 0.741 AC: 349786 AN: 472076

Other (OTH) AF: 0.730 AC: 23006 AN: 31502

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.777 AC: 106353 AN: 136848 Hom.: 42309 Cov.: 0 AF XY: 0.777 AC XY: 51457 AN XY: 66244

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.593 AC: 22573 AN: 38086

American (AMR) AF: 0.860 AC: 11565 AN: 13440

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2746 AN: 3200

East Asian (EAS) AF: 0.806 AC: 3560 AN: 4418

South Asian (SAS) AF: 0.782 AC: 3308 AN: 4230

European-Finnish (FIN) AF: 0.811 AC: 7031 AN: 8668

Middle Eastern (MID) AF: 0.833 AC: 205 AN: 246

European-Non Finnish (NFE) AF: 0.859 AC: 53159 AN: 61898

Other (OTH) AF: 0.810 AC: 1511 AN: 1866

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.803 Hom.: 3906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53
Mutation Taster		=168/32	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35575803; hg19: chr19-20807177; COSMIC: COSV74128862; COSMIC: COSV74128862;