19-53553902-C-G

Variant names:

• chr19-53553902-C-G
• rs7248353
• NM_001079906.2:c.-137-1943C>G

Variant summary

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

The NM_001079906.2(ZNF331):​c.-137-1943C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,090 control chromosomes in the GnomAD database, including 42,610 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 0.74 (42610 hom., cov: 32)
• Consequence: ZNF331 NM_001079906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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 = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.-137-1943C>G		intron_variant	Intron 2 of 5	ENST00000449416.6	NP_001073375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6	c.-137-1943C>G		intron_variant	Intron 2 of 5	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112564 AN: 151972 Hom.: 42562 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.741 AC: 112674 AN: 152090 Hom.: 42610 Cov.: 32 AF XY: 0.733 AC XY: 54467 AN XY: 74340

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.735

Alfa AF: 0.724 Hom.: 5053

Bravo AF: 0.749

Asia WGS AF: 0.690 AC: 2401 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	3.2
DANN	Benign	0.50

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: rs7248353; hg19: chr19-54057156;