rs3745178

Positions:

• chr19-53091553-A-G
• chr19-53091553-A-T

Variant summary

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

The ENST00000355147.9(ZNF160):​c.-186T>C variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,442 control chromosomes in the GnomAD database, including 9,520 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9518 hom., cov: 30)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: ZNF160 ENST00000355147.9 splice_region, 5_prime_UTR
• Scores: Splicing: ADA: 0.00001863
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

Genes affected

ZNF160 (HGNC:12948): (zinc finger protein 160) The protein encoded by this gene is a Kruppel-related zinc finger protein which is characterized by the presence of an N-terminal repressor domain, the Kruppel-associated box (KRAB). The KRAB domain is a potent repressor of transcription; thus this protein may function in transcription regulation. Multiple transcript variants have been found for this gene. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF160	NM_001322131.2	c.-186T>C		5_prime_UTR_variant	2/6	ENST00000683776.1	NP_001309060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF160	ENST00000683776.1	c.-186T>C		5_prime_UTR_variant	2/6		NM_001322131.2	ENSP00000507845	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52843 AN: 151282 Hom.: 9511 Cov.: 30

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.227 AC: 10 AN: 44 Hom.: 2 Cov.: 0 AF XY: 0.281 AC XY: 9 AN XY: 32

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.190

GnomAD4 genome AF: 0.349 AC: 52868 AN: 151398 Hom.: 9518 Cov.: 30 AF XY: 0.344 AC XY: 25474 AN XY: 73958

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.346

Alfa AF: 0.263 Hom.: 1060

Bravo AF: 0.351

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.6
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0040
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: rs3745178; hg19: chr19-53594806;