19-53091553-A-G

Variant names:

• chr19-53091553-A-G
• rs3745178
• ENST00000355147.9:c.-186T>C

Variant summary

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

The ENST00000355147.9(ZNF160):​c.-186T>C variant causes a splice region 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
• Scores: Splicing: ADA: 0.00001863
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF160	NM_001322131.2	c.-186T>C		5_prime_UTR_variant	Exon 2 of 6	ENST00000683776.1	NP_001309060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF160	ENST00000683776.1	c.-186T>C		5_prime_UTR_variant	Exon 2 of 6		NM_001322131.2	ENSP00000507845.1

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

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) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.190 AC: 8 AN: 42

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.387 AC: 15952 AN: 41230

American (AMR) AF: 0.288 AC: 4393 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1167 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1154 AN: 5088

South Asian (SAS) AF: 0.370 AC: 1773 AN: 4786

European-Finnish (FIN) AF: 0.280 AC: 2935 AN: 10492

Middle Eastern (MID) AF: 0.331 AC: 96 AN: 290

European-Non Finnish (NFE) AF: 0.360 AC: 24446 AN: 67812

Other (OTH) AF: 0.346 AC: 725 AN: 2094

Alfa AF: 0.281 Hom.: 1427

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
PhyloP100		-0.089
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3745178; hg19: chr19-53594806;