5-179080269-A-G

Variant names:

• chr5-179080269-A-G
• rs1445844
• NM_014594.3:c.*172A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014594.3(ZNF354C):​c.*172A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 430,724 control chromosomes in the GnomAD database, including 107,434 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 0.71 (38907 hom., cov: 33)
  • Exomes 𝑓: 0.70 (68527 hom.)
• Consequence: ZNF354C NM_014594.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 11 publications found

Genes affected

ZNF354C (HGNC:16736): (zinc finger protein 354C) 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. Located in nucleoplasm. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF354C	NM_014594.3	c.*172A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000315475.7	NP_055409.1
ZNF354C	XM_017009409.2	c.*172A>G		3_prime_UTR_variant	Exon 5 of 5		XP_016864898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF354C	ENST00000315475.7	c.*172A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_014594.3	ENSP00000324064.6

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108457 AN: 152012 Hom.: 38878 Cov.: 33

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.697 AC: 194050 AN: 278596 Hom.: 68527 Cov.: 4 AF XY: 0.698 AC XY: 99283 AN XY: 142222

African (AFR) AF: 0.743 AC: 5507 AN: 7408

American (AMR) AF: 0.712 AC: 7145 AN: 10040

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 6732 AN: 9074

East Asian (EAS) AF: 0.883 AC: 19791 AN: 22422

South Asian (SAS) AF: 0.841 AC: 7737 AN: 9202

European-Finnish (FIN) AF: 0.660 AC: 15328 AN: 23228

Middle Eastern (MID) AF: 0.760 AC: 945 AN: 1244

European-Non Finnish (NFE) AF: 0.664 AC: 118702 AN: 178762

Other (OTH) AF: 0.706 AC: 12163 AN: 17216

GnomAD4 genome AF: 0.713 AC: 108542 AN: 152128 Hom.: 38907 Cov.: 33 AF XY: 0.719 AC XY: 53468 AN XY: 74370

African (AFR) AF: 0.744 AC: 30882 AN: 41514

American (AMR) AF: 0.733 AC: 11197 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2585 AN: 3468

East Asian (EAS) AF: 0.887 AC: 4600 AN: 5184

South Asian (SAS) AF: 0.842 AC: 4064 AN: 4824

European-Finnish (FIN) AF: 0.685 AC: 7245 AN: 10572

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45490 AN: 67976

Other (OTH) AF: 0.745 AC: 1573 AN: 2110

Alfa AF: 0.689 Hom.: 54992

Bravo AF: 0.717

Asia WGS AF: 0.850 AC: 2948 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.85
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs1445844; hg19: chr5-178507270;