19-53578661-A-G

Position:

• chr19-53578661-A-G

Variant summary

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

The NM_001079906.2(ZNF331):​c.*709A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 205,582 control chromosomes in the GnomAD database, including 57,092 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 0.75 (43252 hom., cov: 31)
  • Exomes 𝑓: 0.71 (13840 hom.)
• Consequence: ZNF331 NM_001079906.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.*709A>G		3_prime_UTR_variant	6/6	ENST00000449416.6	NP_001073375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6	c.*709A>G		3_prime_UTR_variant	6/6	5	NM_001079906.2	ENSP00000393817	P1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113502 AN: 151480 Hom.: 43210 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.743

GnomAD4 exome AF: 0.713 AC: 38489 AN: 53980 Hom.: 13840 Cov.: 0 AF XY: 0.710 AC XY: 17804 AN XY: 25082

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.749 AC: 113609 AN: 151602 Hom.: 43252 Cov.: 31 AF XY: 0.743 AC XY: 55014 AN XY: 74038

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.743

Alfa AF: 0.722 Hom.: 38626

Bravo AF: 0.755

Asia WGS AF: 0.697 AC: 2422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8110350; hg19: chr19-54081915;