NM_001099694.2:c.-121-14129G>T

Variant names:

• chr19-52477195-G-T
• rs10422173
• NM_001099694.2:c.-121-14129G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001099694.2(ZNF578):​c.-121-14129G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 152,268 control chromosomes in the GnomAD database, including 6 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 0.0053 (6 hom., cov: 32)
• Consequence: ZNF578 NM_001099694.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 1 publications found

Genes affected

ZNF578 (HGNC:26449): (zinc finger protein 578) 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 located in cytoplasm. Predicted to be active 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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0053 (807/152268) while in subpopulation AFR AF = 0.0189 (785/41546). AF 95% confidence interval is 0.0178. There are 6 homozygotes in GnomAd4. There are 379 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF578	NM_001099694.2	c.-121-14129G>T		intron_variant	Intron 2 of 5	ENST00000421239.7	NP_001093164.1
ZNF578	NM_001366182.2	c.-20+20237G>T		intron_variant	Intron 3 of 5		NP_001353111.1
ZNF578	XM_047438189.1	c.-20+20237G>T		intron_variant	Intron 2 of 4		XP_047294145.1
ZNF578	XM_047438194.1	c.-100+20237G>T		intron_variant	Intron 2 of 3		XP_047294150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF578	ENST00000421239.7	c.-121-14129G>T		intron_variant	Intron 2 of 5	2	NM_001099694.2	ENSP00000459216.1

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 808 AN: 152150 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00530 AC: 807 AN: 152268 Hom.: 6 Cov.: 32 AF XY: 0.00509 AC XY: 379 AN XY: 74452

African (AFR) AF: 0.0189 AC: 785 AN: 41546

American (AMR) AF: 0.00111 AC: 17 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00458 Hom.: 1

Bravo AF: 0.00594

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.37
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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: rs10422173; hg19: chr19-52980448;