11-6955753-G-A

Position:

• chr11-6955753-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_013250.4(ZNF215):​c.776G>A​(p.Ser259Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,607,596 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (45 hom.)
• Consequence: ZNF215 NM_013250.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00449273).
• BP6: Variant 11-6955753-G-A is Benign according to our data. Variant chr11-6955753-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF215	NM_013250.4	c.776G>A	p.Ser259Asn	missense_variant	7/7	ENST00000278319.10	NP_037382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10	c.776G>A	p.Ser259Asn	missense_variant	7/7	1	NM_013250.4	ENSP00000278319.5

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 725 AN: 152156 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00813

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00473 AC: 1159 AN: 245178 Hom.: 4 AF XY: 0.00522 AC XY: 691 AN XY: 132282

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00237

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00790

Gnomad FIN exome AF: 0.00163

Gnomad NFE exome AF: 0.00702

Gnomad OTH exome AF: 0.00404

GnomAD4 exome AF: 0.00709 AC: 10319 AN: 1455322 Hom.: 45 Cov.: 29 AF XY: 0.00727 AC XY: 5263 AN XY: 723636

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.00185

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00850

Gnomad4 FIN exome AF: 0.00193

Gnomad4 NFE exome AF: 0.00803

Gnomad4 OTH exome AF: 0.00632

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152274 Hom.: 2 Cov.: 32 AF XY: 0.00431 AC XY: 321 AN XY: 74448

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00813

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00661 Hom.: 6

Bravo AF: 0.00454

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00698 AC: 60

ExAC AF: 0.00502 AC: 610

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00671

EpiControl AF: 0.00563

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.92
DANN	Benign	0.73
DEOGEN2	Benign	0.0069	T;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.56	.;T;T;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0045	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L;L;L;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.11	N;.;N;N
REVEL	Benign	0.091
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0020	B;.;B;.
Vest4		0.031
MVP		0.16
MPC		0.0060
ClinPred		0.0059	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.044

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

Other links and lift over

dbSNP: rs117380100; hg19: chr11-6976984;