Genetic Variant NM_013249.4:c.1091G>T (chr11-7000592-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_013249.4(ZNF214):c.1091G>T(p.Gly364Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,458,258 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: 0.0000055 ( 0 hom. )

Consequence

ZNF214
NM_013249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

ZNF214 (HGNC:13006): (zinc finger protein 214) This gene is expressed predominantly in the testis and encodes a zinc finger protein that contains an N-terminal kruppel-associated box A (KRABA) domain and twelve 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]

ZNF214 links:

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:

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ACMG classification

Classification made for transcript

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
ZNF214	NM_013249.4 link	c.1091G>T	p.Gly364Val	missense_variant	Exon 3 of 3	ENST00000278314.5	NP_037381.2	Q9UL59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF214	ENST00000278314.5 link	c.1091G>T	p.Gly364Val	missense_variant	Exon 3 of 3	1	NM_013249.4	ENSP00000278314.4	Q9UL59
ZNF214	ENST00000536068.5 link	c.1091G>T	p.Gly364Val	missense_variant	Exon 4 of 4	1		ENSP00000445373.1	Q9UL59
ZNF215	ENST00000636606.1 link	n.*676C>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000490359.1	A0A1B0GV37
ZNF215	ENST00000636606.1 link	n.*676C>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000490359.1	A0A1B0GV37

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1458258

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725344

show subpopulations

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.37

.;T

M_CAP

Benign

0.0030

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

H;H

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-8.2

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.94

P;P

Vest4

0.37

MutPred

0.65

Loss of disorder (P = 0.0477);Loss of disorder (P = 0.0477);

MVP

0.64

MPC

0.10

ClinPred

0.97

GERP RS

2.5

Varity_R

0.75

gMVP

0.075

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over