14-88385823-ATGGCAGCCGGAGAGGTAAAGGGCAGC-A

Position:

• chr14-88385823-ATGGCAGCCGGAGAGGTAAAGGGCAGC-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_018418.5(SPATA7):​c.8_19+14del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPATA7 NM_018418.5 splice_donor, splice_donor_5th_base, coding_sequence, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.94

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-88385823-ATGGCAGCCGGAGAGGTAAAGGGCAGC-A is Pathogenic according to our data. Variant chr14-88385823-ATGGCAGCCGGAGAGGTAAAGGGCAGC-A is described in ClinVar as [Pathogenic]. Clinvar id is 801396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-88385823-ATGGCAGCCGGAGAGGTAAAGGGCAGC-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA7	NM_018418.5	c.8_19+14del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	1/12	ENST00000393545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA7	ENST00000393545.9	c.8_19+14del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	1/12	1	NM_018418.5	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453414 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 722056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1595158200; hg19: chr14-88852167;