rs8100338

Positions:

• chr19-53521940-C-G

Variant summary

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

The ENST00000253144.13(ZNF331):​c.-417C>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 0.319 in 151,996 control chromosomes in the GnomAD database, including 7,895 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 (7887 hom., cov: 32)
  • Exomes 𝑓: 0.47 (8 hom.)
• Consequence: ZNF331 ENST00000253144.13 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.9).
• 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.-379C>G		5_prime_UTR_variant	1/7		NP_001304049.1
ZNF331	NM_018555.6	c.-417C>G		5_prime_UTR_variant	1/7		NP_061025.5
ZNF331	XM_011527076.4	c.-848C>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.-417C>G		5_prime_UTR_variant	1/7	1		ENSP00000253144	P1
ZNF331	ENST00000502248.5	c.-379C>G		5_prime_UTR_variant	1/7	1		ENSP00000423675
ZNF331	ENST00000511593.6	c.-380C>G		5_prime_UTR_variant	1/7	5		ENSP00000427439	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48483 AN: 151810 Hom.: 7884 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.471 AC: 32 AN: 68 Hom.: 8 Cov.: 0 AF XY: 0.405 AC XY: 17 AN XY: 42

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.319 AC: 48497 AN: 151928 Hom.: 7887 Cov.: 32 AF XY: 0.320 AC XY: 23751 AN XY: 74260

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.346

Alfa AF: 0.300 Hom.: 909

Bravo AF: 0.326

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	-0.90
CADD	Benign	0.59
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8100338; hg19: chr19-54025194; COSMIC: COSV53477592;