rs8100275

Positions:

• chr19-53247262-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182609.4(ZNF677):​c.16-3365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,866 control chromosomes in the GnomAD database, including 8,750 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 0.31 (8750 hom., cov: 31)
• Consequence: ZNF677 NM_182609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

Genes affected

ZNF677 (HGNC:28730): (zinc finger protein 677) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF677	NM_182609.4	c.16-3365C>T		intron_variant		ENST00000598513.6	NP_872415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF677	ENST00000598513.6	c.16-3365C>T		intron_variant		1	NM_182609.4	ENSP00000469391	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47660 AN: 151748 Hom.: 8728 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0494

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.314 AC: 47728 AN: 151866 Hom.: 8750 Cov.: 31 AF XY: 0.308 AC XY: 22837 AN XY: 74202

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0495

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.327

Alfa AF: 0.301 Hom.: 1165

Bravo AF: 0.323

Asia WGS AF: 0.163 AC: 570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs8100275; hg19: chr19-53750515;