11-6932630-G-T

Variant names:

• chr11-6932630-G-T
• NM_013250.4:c.358G>T

Variant summary

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

The NM_001354855.2(ZNF215):​c.-188G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF215 NM_001354855.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

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.358G>T	p.Val120Leu	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.358G>T	p.Val120Leu	missense_variant	Exon 3 of 7	1	NM_013250.4	ENSP00000278319.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461650 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727122

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;.;T;.
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.77	.;T;T;.
M_CAP	Benign	0.0028	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M;M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N;.;N;D
REVEL	Benign	0.12
Sift	Uncertain	0.013	D;.;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.043	B;.;B;.
Vest4		0.26
MutPred		0.70		Gain of ubiquitination at K117 (P = 0.0719);Gain of ubiquitination at K117 (P = 0.0719);Gain of ubiquitination at K117 (P = 0.0719);Gain of ubiquitination at K117 (P = 0.0719);
MVP		0.36
MPC		0.0086
ClinPred		0.82	D
GERP RS		0.44
Varity_R		0.29
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-6953861;