dbSNP rs924900: ZNF713:c.-582-7C>G (chr7-55906246-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182633.3(ZNF713):c.-582-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 152,224 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.045 ( 293 hom., cov: 32)

Exomes 𝑓: 0.050 ( 0 hom. )

Consequence

ZNF713
NM_182633.3 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

Publications

2 publications found

Variant links:

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

ZNF713 links:

ENSG00000249773 (HGNC:):

ENSG00000249773 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF713	NM_182633.3 link	c.-582-7C>G		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000429591.4	NP_872439.2	Q8N859
ZNF713	NM_001366796.2 link	c.-589-7C>G		splice_region_variant, intron_variant	Intron 1 of 6		NP_001353725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF713	ENST00000429591.4 link	c.-582-7C>G		splice_region_variant, intron_variant	Intron 1 of 6	5	NM_182633.3	ENSP00000416662.3		Q8N859
ENSG00000249773	ENST00000426595.1 link	c.-589-7C>G		splice_region_variant, intron_variant	Intron 1 of 7	5		ENSP00000390331.1		I3L0E3

Frequencies

GnomAD3 genomes

AF:

0.0448

AC:

6814

AN:

152086

Hom.:

294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00995

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0443

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.0801

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0420

Gnomad OTH

AF:

0.0421

GnomAD4 exome

AF:

0.0500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0714

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0448

AC:

6813

AN:

152204

Hom.:

293

Cov.:

AF XY:

0.0496

AC XY:

3692

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00992

AC:

412

AN:

41544

American (AMR)

AF:

0.0444

AC:

678

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3472

East Asian (EAS)

AF:

0.219

AC:

1132

AN:

5168

South Asian (SAS)

AF:

0.0796

AC:

384

AN:

4826

European-Finnish (FIN)

AF:

0.104

AC:

1097

AN:

10588

Middle Eastern (MID)

AF:

0.0411

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0420

AC:

2855

AN:

68010

Other (OTH)

AF:

0.0426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

326

652

978

1304

1630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0450

Hom.:

Bravo

AF:

0.0380

Asia WGS

AF:

0.112

AC:

388

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.58

PhyloP100

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over