rs1543922

Positions:

• chr19-51581583-C-T

Variant summary

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

The NM_007147.4(ZNF175):​c.199+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,570,738 control chromosomes in the GnomAD database, including 4,967 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 0.11 (2209 hom., cov: 32)
  • Exomes 𝑓: 0.025 (2758 hom.)
• Consequence: ZNF175 NM_007147.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

ZNF175 (HGNC:12964): (zinc finger protein 175) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in cytosol; intermediate filament cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF175	NM_007147.4	c.199+66C>T		intron_variant		ENST00000262259.7	NP_009078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF175	ENST00000262259.7	c.199+66C>T		intron_variant		1	NM_007147.4	ENSP00000262259	P1
ZNF175	ENST00000436511.2	c.199+66C>T		intron_variant		2		ENSP00000440578
ZNF175	ENST00000600460.1	n.150+66C>T		intron_variant, non_coding_transcript_variant		2
ZNF175	ENST00000596504.1			downstream_gene_variant		2		ENSP00000470922

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16599 AN: 152044 Hom.: 2207 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00866

Gnomad OTH AF: 0.0877

GnomAD4 exome AF: 0.0249 AC: 35379 AN: 1418576 Hom.: 2758 Cov.: 31 AF XY: 0.0235 AC XY: 16443 AN XY: 700462

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.0924

Gnomad4 ASJ exome AF: 0.00976

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.0247

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.00753

Gnomad4 OTH exome AF: 0.0452

GnomAD4 genome AF: 0.109 AC: 16622 AN: 152162 Hom.: 2209 Cov.: 32 AF XY: 0.110 AC XY: 8155 AN XY: 74394

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.00866

Gnomad4 OTH AF: 0.0868

Alfa AF: 0.0265 Hom.: 528

Bravo AF: 0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1543922; hg19: chr19-52084836; COSMIC: COSV51794522; COSMIC: COSV51794522;