rs612578

Variant names:

• chr19-20661070-A-G
• rs612578
• NM_001076675.3:c.3+374T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001076675.3(ZNF626):​c.3+374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,144 control chromosomes in the GnomAD database, including 4,098 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4098 hom., cov: 33)
• Consequence: ZNF626 NM_001076675.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

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.3+374T>C		intron	N/A	NP_001070143.1	Q68DY1-1
	ZNF626	NM_145297.4		c.3+374T>C		intron	N/A	NP_660340.1	Q68DY1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	ENST00000601440.6	TSL:4 MANE Select	c.3+374T>C		intron	N/A	ENSP00000469958.1	Q68DY1-1
	ZNF626	ENST00000291750.6	TSL:1	c.3+374T>C		intron	N/A	ENSP00000291750.6	Q68DY1-3
	ZNF626	ENST00000595405.1	TSL:3	c.-3+374T>C		intron	N/A	ENSP00000469566.1	M0QY39

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32682 AN: 152024 Hom.: 4094 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.215 AC: 32709 AN: 152144 Hom.: 4098 Cov.: 33 AF XY: 0.217 AC XY: 16117 AN XY: 74368

African (AFR) AF: 0.104 AC: 4310 AN: 41534

American (AMR) AF: 0.319 AC: 4883 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1876 AN: 5138

South Asian (SAS) AF: 0.223 AC: 1078 AN: 4828

European-Finnish (FIN) AF: 0.212 AC: 2248 AN: 10584

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16943 AN: 67990

Other (OTH) AF: 0.224 AC: 475 AN: 2116

Alfa AF: 0.244 Hom.: 8304

Bravo AF: 0.221

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.16
PhyloP100		-0.64
PromoterAI		0.072	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs612578; hg19: chr19-20843876;