chr19-53163407-G-A

Position:

• chr19-53163407-G-A

Variant summary

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

The NM_024733.5(ZNF665):​c.*1046C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,062 control chromosomes in the GnomAD database, including 22,956 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 0.52 (22954 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: ZNF665 NM_024733.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF665	NM_024733.5	c.*1046C>T		3_prime_UTR_variant	4/4	ENST00000396424.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF665	ENST00000396424.5	c.*1046C>T		3_prime_UTR_variant	4/4	2	NM_024733.5	P1
	ENST00000600257.1	n.203G>A		non_coding_transcript_exon_variant	2/2	3
ZNF665	ENST00000596564.1	n.50+443C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78459 AN: 151940 Hom.: 22942 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.516 AC: 78500 AN: 152056 Hom.: 22954 Cov.: 32 AF XY: 0.524 AC XY: 38951 AN XY: 74294

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.520

Alfa AF: 0.591 Hom.: 26848

Bravo AF: 0.497

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1133146; hg19: chr19-53666660;