19-53576890-A-G

Variant names:

• chr19-53576890-A-G
• rs8109631
• NM_001079906.2:c.330A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001079906.2(ZNF331):​c.330A>G​(p.Arg110Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,613,858 control chromosomes in the GnomAD database, including 417,751 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 (43648 hom., cov: 31)
  • Exomes 𝑓: 0.71 (374103 hom.)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 24 publications found

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]

ENSG00000290755 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.643 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079906.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	NM_001079906.2	MANE Select	c.330A>G	p.Arg110Arg	synonymous	Exon 6 of 6	NP_001073375.1	Q9NQX6
	ZNF331	NM_001079907.1		c.330A>G	p.Arg110Arg	synonymous	Exon 6 of 6	NP_001073376.1	Q9NQX6
	ZNF331	NM_001253798.2		c.330A>G	p.Arg110Arg	synonymous	Exon 7 of 7	NP_001240727.1	Q9NQX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	ENST00000449416.6	TSL:5 MANE Select	c.330A>G	p.Arg110Arg	synonymous	Exon 6 of 6	ENSP00000393817.1	Q9NQX6
	ZNF331	ENST00000253144.13	TSL:1	c.330A>G	p.Arg110Arg	synonymous	Exon 7 of 7	ENSP00000253144.9	Q9NQX6
	ZNF331	ENST00000504493.6	TSL:1	c.330A>G	p.Arg110Arg	synonymous	Exon 5 of 5	ENSP00000425517.2	Q9NQX6

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114141 AN: 151914 Hom.: 43608 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.697 AC: 175239 AN: 251376 AF XY: 0.700

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.671

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.720

Gnomad OTH exome AF: 0.709

GnomAD4 exome AF: 0.714 AC: 1043547 AN: 1461826 Hom.: 374103 Cov.: 58 AF XY: 0.714 AC XY: 518976 AN XY: 727216

African (AFR) AF: 0.895 AC: 29962 AN: 33480

American (AMR) AF: 0.575 AC: 25699 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 18160 AN: 26134

East Asian (EAS) AF: 0.707 AC: 28076 AN: 39700

South Asian (SAS) AF: 0.694 AC: 59892 AN: 86254

European-Finnish (FIN) AF: 0.667 AC: 35635 AN: 53418

Middle Eastern (MID) AF: 0.708 AC: 4083 AN: 5768

European-Non Finnish (NFE) AF: 0.718 AC: 798787 AN: 1111970

Other (OTH) AF: 0.716 AC: 43253 AN: 60396

GnomAD4 genome AF: 0.751 AC: 114244 AN: 152032 Hom.: 43648 Cov.: 31 AF XY: 0.745 AC XY: 55335 AN XY: 74288

African (AFR) AF: 0.891 AC: 36988 AN: 41496

American (AMR) AF: 0.664 AC: 10129 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2407 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3492 AN: 5160

South Asian (SAS) AF: 0.700 AC: 3369 AN: 4816

European-Finnish (FIN) AF: 0.655 AC: 6909 AN: 10552

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48674 AN: 67972

Other (OTH) AF: 0.747 AC: 1579 AN: 2114

Alfa AF: 0.733 Hom.: 126031

Bravo AF: 0.756

Asia WGS AF: 0.704 AC: 2449 AN: 3478

EpiCase AF: 0.714

EpiControl AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.58
PhyloP100		-0.64
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8109631; hg19: chr19-54080144; COSMIC: COSV53475694; COSMIC: COSV53475694;