10-45015960-A-G

Variant names:

• chr10-45015960-A-G
• rs6593456
• ENST00000456938.7:n.683+2T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000456938.7(ZNF22-AS1):​n.683+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,158 control chromosomes in the GnomAD database, including 39,995 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 0.72 (39994 hom., cov: 33)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: ZNF22-AS1 ENST00000456938.7 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75
• Publications: 5 publications found

Genes affected

ZNF22-AS1 (HGNC:23509): (ZNF22 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF22-AS1	ENST00000456938.7	n.683+2T>C		splice_donor_variant, intron_variant	Intron 6 of 6	1
ZNF22-AS1	ENST00000745469.1	n.399T>C		non_coding_transcript_exon_variant	Exon 4 of 4
ZNF22-AS1	ENST00000717566.1	n.598-15544T>C		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110097 AN: 152034 Hom.: 39965 Cov.: 33

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

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) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.724 AC: 110179 AN: 152152 Hom.: 39994 Cov.: 33 AF XY: 0.726 AC XY: 53990 AN XY: 74360

African (AFR) AF: 0.745 AC: 30906 AN: 41500

American (AMR) AF: 0.766 AC: 11706 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2748 AN: 5162

South Asian (SAS) AF: 0.723 AC: 3490 AN: 4824

European-Finnish (FIN) AF: 0.745 AC: 7879 AN: 10578

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48966 AN: 68012

Other (OTH) AF: 0.723 AC: 1528 AN: 2114

Alfa AF: 0.720 Hom.: 66743

Bravo AF: 0.728

Asia WGS AF: 0.679 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.027
DANN	Benign	0.34
PhyloP100		-4.8

Splicing

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

Other links and lift over

dbSNP: rs6593456; hg19: chr10-45511408;