7-55923247-G-A

Position:

• chr7-55923247-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182633.3(ZNF713):​c.173G>A​(p.Arg58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ZNF713 NM_182633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.787

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]

ENSG00000249773 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26837188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF713	NM_182633.3	c.173G>A	p.Arg58Gln	missense_variant	5/7	ENST00000429591.4	NP_872439.2
ZNF713	NM_001366796.2	c.134G>A	p.Arg45Gln	missense_variant	5/7		NP_001353725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF713	ENST00000429591.4	c.173G>A	p.Arg58Gln	missense_variant	5/7	5	NM_182633.3	ENSP00000416662.3
ENSG00000249773	ENST00000426595.1	c.134G>A	p.Arg45Gln	missense_variant	5/8	5		ENSP00000390331.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461548 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727080

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: 0.0000216

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.134G>A (p.R45Q) alteration is located in exon 2 (coding exon 2) of the ZNF713 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	.;.;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.15	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.023	D;.;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.32
MutPred		0.69		Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);
MVP		0.18
MPC		0.72
ClinPred		0.87	D
GERP RS		2.0
Varity_R		0.19
gMVP		0.12

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: rs1786028391; hg19: chr7-55990940;