16-3138779-C-T

Variant names:

• chr16-3138779-C-T
• rs35190304
• NM_004220.3:c.558C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004220.3(ZNF213):​c.558C>T​(p.Pro186Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,614,008 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (58 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (61 hom.)
• Consequence: ZNF213 NM_004220.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0930
• Publications: 0 publications found

Genes affected

ZNF213 (HGNC:13005): (zinc finger protein 213) C2H2 zinc finger proteins, such as ZNF213, have bipartite structures in which one domain binds DNA or RNA and the other modulates target gene expression.[supplied by OMIM, Apr 2004]

ZNF213-AS1 (HGNC:50505): (ZNF213 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 16-3138779-C-T is Benign according to our data. Variant chr16-3138779-C-T is described in ClinVar as [Benign]. Clinvar id is 776968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.093 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2150/152274) while in subpopulation AFR AF = 0.0495 (2055/41550). AF 95% confidence interval is 0.0477. There are 58 homozygotes in GnomAd4. There are 1003 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF213	NM_004220.3	c.558C>T	p.Pro186Pro	synonymous_variant	Exon 4 of 6	ENST00000396878.8	NP_004211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF213	ENST00000396878.8	c.558C>T	p.Pro186Pro	synonymous_variant	Exon 4 of 6	1	NM_004220.3	ENSP00000380087.3

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2146 AN: 152154 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00366 AC: 919 AN: 251262 AF XY: 0.00274

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.00206

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00143 AC: 2089 AN: 1461734 Hom.: 61 Cov.: 32 AF XY: 0.00123 AC XY: 893 AN XY: 727186

African (AFR) AF: 0.0512 AC: 1714 AN: 33464

American (AMR) AF: 0.00264 AC: 118 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111966

Other (OTH) AF: 0.00295 AC: 178 AN: 60386

GnomAD4 genome AF: 0.0141 AC: 2150 AN: 152274 Hom.: 58 Cov.: 33 AF XY: 0.0135 AC XY: 1003 AN XY: 74446

African (AFR) AF: 0.0495 AC: 2055 AN: 41550

American (AMR) AF: 0.00373 AC: 57 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68014

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.0139 Hom.: 34

Bravo AF: 0.0174

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.5
DANN	Benign	0.67
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35190304; hg19: chr16-3188780;