rs7246435

Positions:

• chr19-53239881-T-C

Variant summary

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

The NM_182609.4(ZNF677):​c.170-1324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,116 control chromosomes in the GnomAD database, including 11,285 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 0.34 (11284 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: ZNF677 NM_182609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF677	NM_182609.4	c.170-1324A>G		intron_variant		ENST00000598513.6	NP_872415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF677	ENST00000598513.6	c.170-1324A>G		intron_variant		1	NM_182609.4	ENSP00000469391	P1
ZNF677	ENST00000594517.5	c.170-1324A>G		intron_variant		1		ENSP00000472416
ZNF677	ENST00000333952.8	c.170-1324A>G		intron_variant		2		ENSP00000334394	P1
ZNF677	ENST00000599328.1	n.1923A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52342 AN: 151984 Hom.: 11254 Cov.: 33

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.345 AC: 52422 AN: 152102 Hom.: 11284 Cov.: 33 AF XY: 0.337 AC XY: 25074 AN XY: 74380

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.347

Alfa AF: 0.279 Hom.: 3078

Bravo AF: 0.356

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.75

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: rs7246435; hg19: chr19-53743134;