NM_013250.4:c.356T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013250.4(ZNF215):c.356T>C(p.Met119Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,872 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M119V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.010 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 21 hom. )

Consequence

ZNF215
NM_013250.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

ZNF215 (HGNC:13007): (zinc finger protein 215) This gene is imprinted in a tissue-specific manner with preferential expression in the testis, and encodes a zinc finger protein that belongs to a family of zinc finger transcription factors. The encoded protein contains an N-terminal SRE-ZBP, Ctfin51, AW-1, and Number 18 (SCAN) domain, a kruppel-associated box A (KRABA) domain, and four C-terminal zinc finger domains. This gene is located within one of three regions on chromosome 11p15 associated with Beckwith-Wiedemann syndrome, called Beckwith-Wiedemann syndrome chromosome region-2 (BWSCR2), and is thought to play a role in the etiology of this disease. [provided by RefSeq, Aug 2017]

ZNF215 links:

LOC107984019 (HGNC:):

LOC107984019 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044968724).

BP6

Variant 11-6932628-T-C is Benign according to our data. Variant chr11-6932628-T-C is described in ClinVar as [Benign]. Clinvar id is 787902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1576/152278) while in subpopulation AFR AF= 0.0361 (1499/41554). AF 95% confidence interval is 0.0346. There are 30 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF215	NM_013250.4 link	c.356T>C	p.Met119Thr	missense_variant	Exon 3 of 7	ENST00000278319.10	NP_037382.2	Q9UL58-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10 link	c.356T>C	p.Met119Thr	missense_variant	Exon 3 of 7	1	NM_013250.4	ENSP00000278319.5		Q9UL58-1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1571

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00264

AC:

660

AN:

250336

Hom.:

AF XY:

0.00193

AC XY:

262

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.00109

AC:

1592

AN:

1461594

Hom.:

Cov.:

AF XY:

0.000916

AC XY:

666

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0384

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.0103

AC:

1576

AN:

152278

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

782

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.0122

ESP6500AA

AF:

0.0368

AC:

162

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00329

AC:

399

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.00069

T;.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.39

.;T;T;.

MetaRNN

Benign

0.0045

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.26

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.80

N;.;N;N

REVEL

Benign

0.088

Sift

Benign

0.043

D;.;D;D

Sift4G

Uncertain

0.018

D;D;D;D

Polyphen

0.0040

B;.;B;.

Vest4

0.15

MVP

0.34

MPC

0.0058

ClinPred

0.0064

GERP RS

4.1

Varity_R

0.14

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over