chr11-7000409-T-C

Variant names:

• chr11-7000409-T-C
• NM_013249.4:c.1274A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013249.4(ZNF214):​c.1274A>G​(p.Gln425Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF214 NM_013249.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227
• Publications: 0 publications found

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]

ZNF215 Gene-Disease associations (from GenCC):

• Beckwith-Wiedemann syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05180511).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013249.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF214	NM_013249.4	MANE Select	c.1274A>G	p.Gln425Arg	missense	Exon 3 of 3	NP_037381.2	Q9UL59
	ZNF214	NM_001354830.2		c.1307A>G	p.Gln436Arg	missense	Exon 4 of 4	NP_001341759.1
	ZNF214	NM_001354831.2		c.1274A>G	p.Gln425Arg	missense	Exon 4 of 4	NP_001341760.1	Q9UL59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF214	ENST00000278314.5	TSL:1 MANE Select	c.1274A>G	p.Gln425Arg	missense	Exon 3 of 3	ENSP00000278314.4	Q9UL59
	ZNF214	ENST00000536068.5	TSL:1	c.1274A>G	p.Gln425Arg	missense	Exon 4 of 4	ENSP00000445373.1	Q9UL59
	ZNF214	ENST00000888786.1		c.1274A>G	p.Gln425Arg	missense	Exon 4 of 4	ENSP00000558845.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461334 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726950

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111674

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.29
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.00086	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.23
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.025
Sift	Benign	1.0	T
Sift4G	Benign	0.53	T
Polyphen		0.013	B
Vest4		0.14
MutPred		0.45		Gain of MoRF binding (P = 0.0165)
MVP		0.26
MPC		0.040
ClinPred		0.053	T
GERP RS		2.2
Varity_R		0.12
gMVP		0.030
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr11-7021640;