chr19-53529790-T-G

Variant names:

• chr19-53529790-T-G
• rs4994351
• ENST00000253144.13:c.-205+7106T>G

Variant summary

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

The ENST00000253144.13(ZNF331):​c.-205+7106T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,224 control chromosomes in the GnomAD database, including 589 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 0.082 (589 hom., cov: 32)
• Consequence: ZNF331 ENST00000253144.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 5 publications found

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000253144.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	NM_001317120.2		c.-235+7706T>G		intron	N/A	NP_001304049.1
	ZNF331	NM_018555.6		c.-205+7106T>G		intron	N/A	NP_061025.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	ENST00000253144.13	TSL:1	c.-205+7106T>G		intron	N/A	ENSP00000253144.9
	ZNF331	ENST00000502248.5	TSL:1	c.-235+7706T>G		intron	N/A	ENSP00000423675.1
	ZNF331	ENST00000511593.6	TSL:5	c.-168+7106T>G		intron	N/A	ENSP00000427439.1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12522 AN: 152106 Hom.: 588 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0781

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0823 AC: 12527 AN: 152224 Hom.: 589 Cov.: 32 AF XY: 0.0805 AC XY: 5993 AN XY: 74418

African (AFR) AF: 0.0574 AC: 2386 AN: 41550

American (AMR) AF: 0.0709 AC: 1084 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 248 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1168 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7322 AN: 68012

Other (OTH) AF: 0.0778 AC: 164 AN: 2108

Alfa AF: 0.0921 Hom.: 1365

Bravo AF: 0.0799

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.44
PhyloP100		-0.0030
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: rs4994351; hg19: chr19-54033044;