rs7246435

Variant names:

• chr19-53239881-T-C
• rs7246435
• NM_182609.4:c.170-1324A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000291131 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF677	NM_182609.4	c.170-1324A>G		intron_variant	Intron 4 of 4	ENST00000598513.6	NP_872415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF677	ENST00000598513.6	c.170-1324A>G		intron_variant	Intron 4 of 4	1	NM_182609.4	ENSP00000469391.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.625 AC: 5 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.608 AC: 25217 AN: 41478

American (AMR) AF: 0.273 AC: 4169 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3472

East Asian (EAS) AF: 0.0508 AC: 263 AN: 5178

South Asian (SAS) AF: 0.254 AC: 1227 AN: 4830

European-Finnish (FIN) AF: 0.217 AC: 2294 AN: 10586

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17343 AN: 67974

Other (OTH) AF: 0.347 AC: 733 AN: 2112

Alfa AF: 0.281 Hom.: 3515

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
PhyloP100		0.56
Mutation Taster		=100/0	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: rs7246435; hg19: chr19-53743134;