11-6932454-G-A

Variant names:

• chr11-6932454-G-A
• rs1564943540
• NM_013250.4:c.182G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013250.4(ZNF215):​c.182G>A​(p.Gly61Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ZNF215 NM_013250.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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]

LOC107984019 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF215	NM_013250.4	c.182G>A	p.Gly61Glu	missense_variant	Exon 3 of 7	ENST00000278319.10	NP_037382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10	c.182G>A	p.Gly61Glu	missense_variant	Exon 3 of 7	1	NM_013250.4	ENSP00000278319.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.182G>A (p.G61E) alteration is located in exon 3 (coding exon 1) of the ZNF215 gene. This alteration results from a G to A substitution at nucleotide position 182, causing the glycine (G) at amino acid position 61 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	.;T;T;.
M_CAP	Benign	0.0024	T
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M;M;M;M
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-7.2	D;.;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D;.;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.037	B;.;B;.
Vest4		0.31
MutPred		0.90		Loss of glycosylation at S60 (P = 0.0575);Loss of glycosylation at S60 (P = 0.0575);Loss of glycosylation at S60 (P = 0.0575);Loss of glycosylation at S60 (P = 0.0575);
MVP		0.62
MPC		0.017
ClinPred		0.85	D
GERP RS		1.9
Varity_R		0.53
gMVP		0.39

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: rs1564943540; hg19: chr11-6953685;