rs9749439

Variant names:

• chr19-57623981-T-G
• rs9749439
• NM_003435.5:c.*2578T>G

Variant summary

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

The NM_003435.5(ZNF134):​c.*2578T>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 0.0788 in 152,232 control chromosomes in the GnomAD database, including 716 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 0.079 (716 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: ZNF134 NM_003435.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 7 publications found

Genes affected

ZNF134 (HGNC:12918): (zinc finger protein 134) Predicted to enable DNA-binding transcription repressor 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 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF134	NM_003435.5	c.*2578T>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000396161.10	NP_003426.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF134	ENST00000396161.10	c.*2578T>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_003435.5	ENSP00000379464.4

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11957 AN: 152106 Hom.: 712 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0818

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0788 AC: 11989 AN: 152222 Hom.: 716 Cov.: 32 AF XY: 0.0798 AC XY: 5939 AN XY: 74436

African (AFR) AF: 0.142 AC: 5892 AN: 41522

American (AMR) AF: 0.124 AC: 1894 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.157 AC: 810 AN: 5172

South Asian (SAS) AF: 0.0483 AC: 233 AN: 4826

European-Finnish (FIN) AF: 0.0221 AC: 234 AN: 10612

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2408 AN: 68014

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0553 Hom.: 423

Bravo AF: 0.0881

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.80
DANN	Benign	0.75
PhyloP100		-1.5

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: rs9749439; hg19: chr19-58135349;