NM_182633.3:c.997C>G

Variant names:

• chr7-55939671-C-G
• NM_182633.3:c.997C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182633.3(ZNF713):​c.997C>G​(p.Leu333Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF713 NM_182633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.737
• Publications: 0 publications found

Genes affected

ZNF713 (HGNC:22043): (zinc finger protein 713) The protein encoded by this gene contains C2H2 zinc finger domains. In some individuals, a CGG-repeat expansion from 5-22 repeats to 68-450 repeats has been identified in the first intron of this gene. This mutation is thought to effect the expression of this gene and it has been proposed that it may be associated with Autistic Spectrum Disorder. [provided by RefSeq, Jul 2016]

ZNF713 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000249773 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26507792).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182633.3. 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
	ZNF713	NM_182633.3	MANE Select	c.997C>G	p.Leu333Val	missense	Exon 7 of 7	NP_872439.2	Q8N859
	ZNF713	NM_001366796.2		c.958C>G	p.Leu320Val	missense	Exon 7 of 7	NP_001353725.1	A0A8I5JYA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF713	ENST00000429591.4	TSL:5 MANE Select	c.997C>G	p.Leu333Val	missense	Exon 7 of 7	ENSP00000416662.3	Q8N859
	ZNF713	ENST00000633730.1	TSL:1	c.958C>G	p.Leu320Val	missense	Exon 4 of 4	ENSP00000487818.1	A0A8I5JYA4
	ENSG00000249773	ENST00000426595.1	TSL:5	c.269-13508C>G		intron	N/A	ENSP00000390331.1	I3L0E3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N
PhyloP100		0.74
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.15
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.092
MutPred		0.57		Gain of MoRF binding (P = 0.0945)
MVP		0.50
MPC		0.65
ClinPred		0.35	T
GERP RS		3.3
Varity_R		0.21
gMVP		0.054
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr7-56007364; COSMIC: COSV70057227;