rs2303222

Variant names:

• chr16-31074149-T-C
• rs2303222
• NM_024706.5:c.-513A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-31074149-T-C
• chr16-31074149-T-A

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 45 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF668	NM_024706.5	MANE Select	c.-513A>G		5_prime_UTR	Exon 1 of 3	NP_078982.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF668	ENST00000300849.5	TSL:1 MANE Select	c.-513A>G		5_prime_UTR	Exon 1 of 3	ENSP00000300849.4	Q96K58-1
	ZNF668	ENST00000921192.1		c.-511A>G		5_prime_UTR	Exon 1 of 3	ENSP00000591251.1
	ZNF668	ENST00000564456.1	TSL:4	n.36A>G		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.833 AC: 5 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.313 AC: 5 AN: 16

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.263 AC: 10941 AN: 41526

American (AMR) AF: 0.416 AC: 6353 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4616 AN: 5174

South Asian (SAS) AF: 0.183 AC: 884 AN: 4824

European-Finnish (FIN) AF: 0.390 AC: 4133 AN: 10590

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26042 AN: 67966

Other (OTH) AF: 0.435 AC: 914 AN: 2102

Alfa AF: 0.386 Hom.: 17974

Bravo AF: 0.381

Asia WGS AF: 0.470 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		-0.17
PromoterAI		0.064	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2303222; hg19: chr16-31085470;