19-53577745-A-G

Variant names:

• chr19-53577745-A-G
• rs1056393
• NM_001079906.2:c.1185A>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.1185A>G​(p.Gly395Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,614,054 control chromosomes in the GnomAD database, including 5,042 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 0.10 (1216 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3826 hom.)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23
• Publications: 9 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=-0.85).
• BP7: Synonymous conserved (PhyloP=-4.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 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.1185A>G	p.Gly395Gly	synonymous	Exon 6 of 6	NP_001073375.1	Q9NQX6
	ZNF331	NM_001079907.1		c.1185A>G	p.Gly395Gly	synonymous	Exon 6 of 6	NP_001073376.1	Q9NQX6
	ZNF331	NM_001253798.2		c.1185A>G	p.Gly395Gly	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.1185A>G	p.Gly395Gly	synonymous	Exon 6 of 6	ENSP00000393817.1	Q9NQX6
	ZNF331	ENST00000253144.13	TSL:1	c.1185A>G	p.Gly395Gly	synonymous	Exon 7 of 7	ENSP00000253144.9	Q9NQX6
	ZNF331	ENST00000504493.6	TSL:1	c.1185A>G	p.Gly395Gly	synonymous	Exon 5 of 5	ENSP00000425517.2	Q9NQX6

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15760 AN: 152066 Hom.: 1217 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0606 AC: 15235 AN: 251376 AF XY: 0.0568

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0675

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0660

Gnomad OTH exome AF: 0.0589

GnomAD4 exome AF: 0.0657 AC: 96009 AN: 1461870 Hom.: 3826 Cov.: 34 AF XY: 0.0634 AC XY: 46097 AN XY: 727244

African (AFR) AF: 0.229 AC: 7669 AN: 33478

American (AMR) AF: 0.0423 AC: 1893 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 1707 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0170 AC: 1466 AN: 86258

European-Finnish (FIN) AF: 0.0523 AC: 2796 AN: 53418

Middle Eastern (MID) AF: 0.0695 AC: 401 AN: 5768

European-Non Finnish (NFE) AF: 0.0682 AC: 75843 AN: 1111998

Other (OTH) AF: 0.0700 AC: 4230 AN: 60396

GnomAD4 genome AF: 0.104 AC: 15778 AN: 152184 Hom.: 1216 Cov.: 33 AF XY: 0.102 AC XY: 7565 AN XY: 74416

African (AFR) AF: 0.220 AC: 9133 AN: 41502

American (AMR) AF: 0.0660 AC: 1009 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4832

European-Finnish (FIN) AF: 0.0531 AC: 564 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4514 AN: 67990

Other (OTH) AF: 0.103 AC: 217 AN: 2112

Alfa AF: 0.0777 Hom.: 1221

Bravo AF: 0.110

Asia WGS AF: 0.0200 AC: 72 AN: 3478

EpiCase AF: 0.0687

EpiControl AF: 0.0717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.60
PhyloP100		-4.2
Mutation Taster		=100/0	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: rs1056393; hg19: chr19-54080999; COSMIC: COSV108056573; COSMIC: COSV108056573;