11-7000578-G-C

Variant names:

• chr11-7000578-G-C
• rs547254936
• NM_013249.4:c.1105C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013249.4(ZNF214):​c.1105C>G​(p.Arg369Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF214 NM_013249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1548414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF214	NM_013249.4	c.1105C>G	p.Arg369Gly	missense_variant	Exon 3 of 3	ENST00000278314.5	NP_037381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF214	ENST00000278314.5	c.1105C>G	p.Arg369Gly	missense_variant	Exon 3 of 3	1	NM_013249.4	ENSP00000278314.4
ZNF214	ENST00000536068.5	c.1105C>G	p.Arg369Gly	missense_variant	Exon 4 of 4	1		ENSP00000445373.1
ZNF215	ENST00000636606.1	n.*662G>C		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000490359.1
ZNF215	ENST00000636606.1	n.*662G>C		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000490359.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000181 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.091
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.47	P;P
Vest4		0.30
MutPred		0.60		Loss of MoRF binding (P = 0.0105);Loss of MoRF binding (P = 0.0105);
MVP		0.45
MPC		0.059
ClinPred		0.72	D
GERP RS		3.4
Varity_R		0.33
gMVP		0.11

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: rs547254936; hg19: chr11-7021809;