rs1048497

Positions:

• chr12-124014995-G-A

Variant summary

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

The NM_152437.3(ZNF664):​c.*2065G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 166,918 control chromosomes in the GnomAD database, including 1,171 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 0.11 (1044 hom., cov: 33)
  • Exomes 𝑓: 0.14 (127 hom.)
• Consequence: ZNF664 NM_152437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

Genes affected

ZNF664 (HGNC:25406): (zinc finger protein 664) 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, DNA-templated. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF664-RFLNA (HGNC:):

RFLNA (HGNC:27051): (refilin A) Predicted to enable filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to be located in cytoplasm. Predicted to be active in actin filament bundle. [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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF664	NM_152437.3	c.*2065G>A		3_prime_UTR_variant	5/5	ENST00000337815.9	NP_689650.1
ZNF664	NM_001204298.2	c.*2065G>A		3_prime_UTR_variant	5/5		NP_001191227.1
ZNF664-RFLNA	NM_001204299.3	c.-234+40975G>A		intron_variant			NP_001191228.1
ZNF664-RFLNA	NM_001347902.2	c.-234+40975G>A		intron_variant			NP_001334831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF664	ENST00000337815.9	c.*2065G>A		3_prime_UTR_variant	5/5	1	NM_152437.3	ENSP00000337320.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16936 AN: 151956 Hom.: 1044 Cov.: 33

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.138 AC: 2047 AN: 14844 Hom.: 127 Cov.: 0 AF XY: 0.139 AC XY: 976 AN XY: 7038

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.111 AC: 16936 AN: 152074 Hom.: 1044 Cov.: 33 AF XY: 0.106 AC XY: 7913 AN XY: 74358

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0583

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.131

Alfa AF: 0.150 Hom.: 2601

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.8
DANN	Benign	0.89

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: rs1048497; hg19: chr12-124499542;