NM_001393938.1:c.142+1481C>G

Variant names:

• chr19-52913715-G-C
• rs8112177
• NM_001393938.1:c.142+1481C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393938.1(ZNF888):​c.142+1481C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 830,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: ZNF888 NM_001393938.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973
• Publications: 0 publications found

Genes affected

ZNF888 (HGNC:38695): (zinc finger protein 888) 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393938.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF888	NM_001393938.1	MANE Select	c.142+1481C>G		intron	N/A	NP_001380867.1
	ZNF888	NM_001384652.1		c.199+1481C>G		intron	N/A	NP_001371581.1
	ZNF888	NM_001310127.2		c.142+1481C>G		intron	N/A	NP_001297056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF888	ENST00000638862.2	TSL:5 MANE Select	c.142+1481C>G		intron	N/A	ENSP00000491567.1
	ZNF888	ENST00000596623.2	TSL:5	n.551+1481C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 830598 Hom.: 0 Cov.: 23 AF XY: 0.00000261 AC XY: 1 AN XY: 383650

African (AFR) AF: 0.00 AC: 0 AN: 15612

American (AMR) AF: 0.00 AC: 0 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5134

East Asian (EAS) AF: 0.00 AC: 0 AN: 3624

South Asian (SAS) AF: 0.00 AC: 0 AN: 16386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1616

European-Non Finnish (NFE) AF: 0.00000132 AC: 1 AN: 759758

Other (OTH) AF: 0.00 AC: 0 AN: 27214

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.26
PhyloP100		-0.97

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

Other links and lift over

dbSNP: rs8112177; hg19: chr19-53416968;