19-53522664-T-C

Position:

• chr19-53522664-T-C

Variant summary

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

The ENST00000253144.13(ZNF331):​c.-225T>C 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 152,160 control chromosomes in the GnomAD database, including 8,004 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 (8002 hom., cov: 32)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: ZNF331 ENST00000253144.13 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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=-0.92).
• 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_018555.6	c.-225T>C		5_prime_UTR_variant	2/7		NP_061025.5
ZNF331	XM_011527076.4	c.-656T>C		5_prime_UTR_variant	2/8		XP_011525378.1
ZNF331	XM_011527078.4	c.-255T>C		5_prime_UTR_variant	2/8		XP_011525380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000253144.13	c.-225T>C		5_prime_UTR_variant	2/7	1		ENSP00000253144	P1
ZNF331	ENST00000502248.5	c.-235+580T>C		intron_variant		1		ENSP00000423675
ZNF331	ENST00000511593.6	c.-188T>C		5_prime_UTR_variant	2/7	5		ENSP00000427439	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48819 AN: 152036 Hom.: 7999 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.321 AC: 48833 AN: 152154 Hom.: 8002 Cov.: 32 AF XY: 0.321 AC XY: 23924 AN XY: 74414

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: 0.286

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.347

Alfa AF: 0.307 Hom.: 2706

Bravo AF: 0.328

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12982082; hg19: chr19-54025918; COSMIC: COSV53479704;