19-53529790-T-G

Variant names:

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

Variant summary

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

The NM_018555.6(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 NM_018555.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001317120.2	c.-235+7706T>G		intron_variant	Intron 1 of 6		NP_001304049.1
ZNF331	NM_018555.6	c.-205+7106T>G		intron_variant	Intron 2 of 6		NP_061025.5
ZNF331	XM_011527076.4	c.-636+7106T>G		intron_variant	Intron 2 of 7		XP_011525378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000253144.13	c.-205+7106T>G		intron_variant	Intron 2 of 6	1		ENSP00000253144.9
ZNF331	ENST00000502248.5	c.-235+7706T>G		intron_variant	Intron 1 of 6	1		ENSP00000423675.1
ZNF331	ENST00000511593.6	c.-168+7106T>G		intron_variant	Intron 2 of 6	5		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

Gnomad4 AFR AF: 0.0574

Gnomad4 AMR AF: 0.0709

Gnomad4 ASJ AF: 0.0716

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0778

Alfa AF: 0.0940 Hom.: 1022

Bravo AF: 0.0799

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs4994351; hg19: chr19-54033044;