19-53537278-G-C

Position:

• chr19-53537278-G-C

Variant summary

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

The NM_018555.6(ZNF331):​c.-204-1938G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,132 control chromosomes in the GnomAD database, including 5,992 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 0.26 (5987 hom., cov: 32)
  • Exomes 𝑓: 0.31 (5 hom.)
• Consequence: ZNF331 NM_018555.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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]

ZNF331 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001317120.2	c.-234-1938G>C		intron_variant			NP_001304049.1
ZNF331	NM_018555.6	c.-204-1938G>C		intron_variant			NP_061025.5
ZNF331	XM_011527076.4	c.-635-47G>C		intron_variant			XP_011525378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000253144.13	c.-204-1938G>C		intron_variant		1		ENSP00000253144.9
ZNF331	ENST00000502248.5	c.-234-1938G>C		intron_variant		1		ENSP00000423675.1
ZNF331	ENST00000511593.6	c.-168+14594G>C		intron_variant		5		ENSP00000427439.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39362 AN: 151950 Hom.: 5966 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.313 AC: 20 AN: 64 Hom.: 5 Cov.: 0 AF XY: 0.328 AC XY: 19 AN XY: 58

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.259 AC: 39418 AN: 152068 Hom.: 5987 Cov.: 32 AF XY: 0.255 AC XY: 18974 AN XY: 74340

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.228

Alfa AF: 0.118 Hom.: 219

Bravo AF: 0.266

Asia WGS AF: 0.259 AC: 897 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	0.40

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: rs8105870; hg19: chr19-54040532;