rs16984547

Variant names:

• chr19-53178789-T-C
• rs16984547
• NM_024733.5:c.16-3218A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF665	NM_024733.5	c.16-3218A>G		intron_variant	Intron 2 of 3	ENST00000396424.5	NP_079009.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF665	ENST00000396424.5	c.16-3218A>G		intron_variant	Intron 2 of 3	2	NM_024733.5	ENSP00000379702.2
ZNF665	ENST00000650736.1	c.16-3218A>G		intron_variant	Intron 3 of 4			ENSP00000498600.1
ZNF665	ENST00000600412.1	c.-53-12442A>G		intron_variant	Intron 1 of 1	5		ENSP00000469154.1

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

African (AFR) AF: 0.123 AC: 5095 AN: 41494

American (AMR) AF: 0.0840 AC: 1282 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4828

European-Finnish (FIN) AF: 0.0759 AC: 803 AN: 10582

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6061 AN: 68000

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0931 Hom.: 1611

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
PhyloP100		0.61
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: rs16984547; hg19: chr19-53682042;