rs16984547

chr19-53178789-T-C

Variant summary

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

The NM_024733.5(ZNF665):c.16-3218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152,140 control chromosomes in the GnomAD database, including 776 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 0.093 (776 hom., cov: 32)
• Consequence: ZNF665 NM_024733.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614

Genes affected

ZNF665 (HGNC:25885): (zinc finger protein 665) 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF665	NM_024733.5	c.16-3218A>G		intron_variant		ENST00000396424.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF665	ENST00000396424.5	c.16-3218A>G		intron_variant		2	NM_024733.5	P1
ZNF665	ENST00000600412.1	c.-53-12442A>G		intron_variant		5
ZNF665	ENST00000650736.1	c.16-3218A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14114 AN: 152022 Hom.: 774 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0927 AC: 14108 AN: 152140 Hom.: 776 Cov.: 32 AF XY: 0.0891 AC XY: 6626 AN XY: 74374

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.0889

Alfa AF: 0.0905 Hom.: 1182

Bravo AF: 0.0987

Asia WGS AF: 0.0170 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.3
Dann	Benign	0.56

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: rs16984547; hg19: chr19-53682042;