14-88391362-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018418.5(SPATA7):c.20-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 1,601,378 control chromosomes in the GnomAD database, including 6,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (499 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6199 hom.)
• Consequence: SPATA7 NM_018418.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600

Genes affected

SPATA7 (HGNC:20423): (spermatogenesis associated 7) This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 14-88391362-T-G is Benign according to our data. Variant chr14-88391362-T-G is described in ClinVar as [Benign]. Clinvar id is 1170459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA7	NM_018418.5	c.20-19T>G		intron_variant		ENST00000393545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA7	ENST00000393545.9	c.20-19T>G		intron_variant		1	NM_018418.5	P2

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10242 AN: 152024 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0724

GnomAD3 exomes AF: 0.0707 AC: 17460 AN: 247078 Hom.: 821 AF XY: 0.0719 AC XY: 9622 AN XY: 133788

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.0979

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0201

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.0838

GnomAD4 exome AF: 0.0868 AC: 125753 AN: 1449236 Hom.: 6199 Cov.: 29 AF XY: 0.0853 AC XY: 61570 AN XY: 721538

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0489

Gnomad4 ASJ exome AF: 0.0971

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0981

Gnomad4 OTH exome AF: 0.0800

GnomAD4 genome AF: 0.0673 AC: 10237 AN: 152142 Hom.: 499 Cov.: 32 AF XY: 0.0657 AC XY: 4884 AN XY: 74390

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0213

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0707

Alfa AF: 0.0903 Hom.: 127

Bravo AF: 0.0608

Asia WGS AF: 0.0120 AC: 44 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber congenital amaurosis 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	8.6
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs75595762; hg19: chr14-88857706;