11-6932628-T-C

Position:

• chr11-6932628-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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 -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/exons	MANE	Protein	UniProt
ZNF215	NM_013250.4	c.356T>C	p.Met119Thr	missense_variant	3/7	ENST00000278319.10	NP_037382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10	c.356T>C	p.Met119Thr	missense_variant	3/7	1	NM_013250.4	ENSP00000278319.5

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1571 AN: 152160 Hom.: 30 Cov.: 32

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.: 11 AF XY: 0.00193 AC XY: 262 AN XY: 135480

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.: 21 Cov.: 31 AF XY: 0.000916 AC XY: 666 AN XY: 727100

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.: 30 Cov.: 32 AF XY: 0.0105 AC XY: 782 AN XY: 74478

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.: 7

Bravo AF: 0.0122

ESP6500AA AF: 0.0368 AC: 162

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00329 AC: 399

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.73
DEOGEN2	Benign	0.00069	T;.;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.39	.;T;T;.
MetaRNN	Benign	0.0045	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.26	N;N;N;N
PrimateAI	Benign	0.38	T
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	T
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

Other links and lift over

dbSNP: rs61729853; hg19: chr11-6953859; COSMIC: COSV99066439;