16-31074149-T-C

Position:

• chr16-31074149-T-C

Variant summary

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

The NM_024706.5(ZNF668):​c.-513A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,170 control chromosomes in the GnomAD database, including 11,563 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 0.37 (11559 hom., cov: 33)
  • Exomes 𝑓: 0.43 (4 hom.)
• Consequence: ZNF668 NM_024706.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

Genes affected

ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator 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]

ZNF646 (HGNC:29004): (zinc finger protein 646) 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. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF668 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF668	NM_024706.5	c.-513A>G		5_prime_UTR_variant	1/3	ENST00000300849.5	NP_078982.3
ZNF646	XM_011545990.3	c.-80+162T>C		intron_variant			XP_011544292.1
ZNF646	XM_047434956.1	c.-80+1207T>C		intron_variant			XP_047290912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF668	ENST00000300849.5	c.-513A>G		5_prime_UTR_variant	1/3	1	NM_024706.5	ENSP00000300849.4
ZNF668	ENST00000564456.1	n.36A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56236 AN: 152024 Hom.: 11559 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.429 AC: 12 AN: 28 Hom.: 4 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.370 AC: 56241 AN: 152142 Hom.: 11559 Cov.: 33 AF XY: 0.370 AC XY: 27501 AN XY: 74378

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.435

Alfa AF: 0.395 Hom.: 13870

Bravo AF: 0.381

Asia WGS AF: 0.470 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2303222; hg19: chr16-31085470;