chr7-55906246-C-G

Position:

• chr7-55906246-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182633.3(ZNF713):​c.-582-7C>G variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZNF713	NM_182633.3	c.-582-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000429591.4	NP_872439.2
ZNF713	NM_001366796.2	c.-589-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001353725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF713	ENST00000429591.4	c.-582-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_182633.3	ENSP00000416662	P2
ZNF713	ENST00000484120.1	n.58C>G		non_coding_transcript_exon_variant	1/2	2
ZNF713	ENST00000411863.2	c.-582-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000416974
ZNF713	ENST00000466630.5	n.206-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6814 AN: 152086 Hom.: 294 Cov.: 32

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: 1 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0448 AC: 6813 AN: 152204 Hom.: 293 Cov.: 32 AF XY: 0.0496 AC XY: 3692 AN XY: 74390

Gnomad4 AFR AF: 0.00992

Gnomad4 AMR AF: 0.0444

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.0796

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0450 Hom.: 17

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
DANN	Benign	0.58

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

LitVar

Other links and lift over

dbSNP: rs924900; hg19: chr7-55973939;