chr19-53522034-C-G

Position:

• chr19-53522034-C-G

Variant summary

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

The ENST00000253144.13(ZNF331):​c.-323C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,902 control chromosomes in the GnomAD database, including 8,000 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 0.32 (8000 hom., cov: 31)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: ZNF331 ENST00000253144.13 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001317120.2	c.-285C>G		5_prime_UTR_variant	1/7		NP_001304049.1
ZNF331	NM_018555.6	c.-323C>G		5_prime_UTR_variant	1/7		NP_061025.5
ZNF331	XM_011527076.4	c.-754C>G		5_prime_UTR_variant	1/8		XP_011525378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000253144.13	c.-323C>G		5_prime_UTR_variant	1/7	1		ENSP00000253144	P1
ZNF331	ENST00000502248.5	c.-285C>G		5_prime_UTR_variant	1/7	1		ENSP00000423675
ZNF331	ENST00000511593.6	c.-286C>G		5_prime_UTR_variant	1/7	5		ENSP00000427439	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48792 AN: 151760 Hom.: 7997 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.333 AC: 8 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.321 AC: 48806 AN: 151878 Hom.: 8000 Cov.: 31 AF XY: 0.322 AC XY: 23899 AN XY: 74236

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.348

Alfa AF: 0.301 Hom.: 912

Bravo AF: 0.328

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.48

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: rs8100455; hg19: chr19-54025288;