rs16985052

Variant names:

• chr19-53577526-C-T
• rs16985052
• NM_001079906.2:c.966C>T

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.966C>T​(p.Thr322Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,613,764 control chromosomes in the GnomAD database, including 5,027 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 (1213 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3814 hom.)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15
• 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=-0.75).
• BP7: Synonymous conserved (PhyloP=-4.15 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.966C>T	p.Thr322Thr	synonymous	Exon 6 of 6	NP_001073375.1	Q9NQX6
	ZNF331	NM_001079907.1		c.966C>T	p.Thr322Thr	synonymous	Exon 6 of 6	NP_001073376.1	Q9NQX6
	ZNF331	NM_001253798.2		c.966C>T	p.Thr322Thr	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.966C>T	p.Thr322Thr	synonymous	Exon 6 of 6	ENSP00000393817.1	Q9NQX6
	ZNF331	ENST00000253144.13	TSL:1	c.966C>T	p.Thr322Thr	synonymous	Exon 7 of 7	ENSP00000253144.9	Q9NQX6
	ZNF331	ENST00000504493.6	TSL:1	c.966C>T	p.Thr322Thr	synonymous	Exon 5 of 5	ENSP00000425517.2	Q9NQX6

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15735 AN: 151768 Hom.: 1214 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0605 AC: 15223 AN: 251438 AF XY: 0.0568

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0675

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0659

Gnomad OTH exome AF: 0.0590

GnomAD4 exome AF: 0.0656 AC: 95949 AN: 1461878 Hom.: 3814 Cov.: 34 AF XY: 0.0634 AC XY: 46078 AN XY: 727238

African (AFR) AF: 0.228 AC: 7647 AN: 33478

American (AMR) AF: 0.0424 AC: 1895 AN: 44724

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

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.0170 AC: 1467 AN: 86258

European-Finnish (FIN) AF: 0.0524 AC: 2797 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0682 AC: 75800 AN: 1111998

Other (OTH) AF: 0.0700 AC: 4229 AN: 60396

GnomAD4 genome AF: 0.104 AC: 15753 AN: 151886 Hom.: 1213 Cov.: 33 AF XY: 0.102 AC XY: 7547 AN XY: 74214

African (AFR) AF: 0.220 AC: 9115 AN: 41406

American (AMR) AF: 0.0662 AC: 1009 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5130

South Asian (SAS) AF: 0.0181 AC: 87 AN: 4802

European-Finnish (FIN) AF: 0.0535 AC: 565 AN: 10566

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

European-Non Finnish (NFE) AF: 0.0663 AC: 4506 AN: 67960

Other (OTH) AF: 0.103 AC: 217 AN: 2104

Alfa AF: 0.0816 Hom.: 534

Bravo AF: 0.110

Asia WGS AF: 0.0200 AC: 72 AN: 3478

EpiCase AF: 0.0686

EpiControl AF: 0.0717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.47
DANN	Benign	0.70
PhyloP100		-4.1
Mutation Taster		=97/3	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: rs16985052; hg19: chr19-54080780; COSMIC: COSV108056572; COSMIC: COSV108056572;