Genetic Variant SPATA7:c.20-19T>G (chr14-88391362-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00600

Publications

5 publications found

Variant links:

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]

SPATA7 Gene-Disease associations (from GenCC):

Leber congenital amaurosis 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
severe early-childhood-onset retinal dystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPATA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SPATA7	NM_018418.5 link	c.20-19T>G		intron_variant	Intron 1 of 11	ENST00000393545.9	NP_060888.2	Q9P0W8-1V9HVY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA7	ENST00000393545.9 link	c.20-19T>G		intron_variant	Intron 1 of 11	1	NM_018418.5	ENSP00000377176.4		Q9P0W8-1

Frequencies

GnomAD3 genomes

AF:

0.0674

AC:

10242

AN:

152024

Hom.:

498

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0707

AC:

17460

AN:

247078

AF XY:

0.0719

show subpopulations

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 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.:

AF XY:

0.0853

AC XY:

61570

AN XY:

721538

show subpopulations

African (AFR)

AF:

0.0132

AC:

440

AN:

33228

American (AMR)

AF:

0.0489

AC:

2181

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.0971

AC:

2528

AN:

26034

East Asian (EAS)

AF:

0.000228

AC:

AN:

39556

South Asian (SAS)

AF:

0.0214

AC:

1831

AN:

85384

European-Finnish (FIN)

AF:

0.104

AC:

5458

AN:

52604

Middle Eastern (MID)

AF:

0.0702

AC:

367

AN:

5226

European-Non Finnish (NFE)

AF:

0.0981

AC:

108144

AN:

1102682

Other (OTH)

AF:

0.0800

AC:

4795

AN:

59938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5435

10871

16306

21742

27177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0673

AC:

10237

AN:

152142

Hom.:

499

Cov.:

AF XY:

0.0657

AC XY:

4884

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0177

AC:

733

AN:

41514

American (AMR)

AF:

0.0575

AC:

879

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0934

AC:

324

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0213

AC:

103

AN:

4828

European-Finnish (FIN)

AF:

0.102

AC:

1082

AN:

10574

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6898

AN:

67984

Other (OTH)

AF:

0.0707

AC:

149

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

479

957

1436

1914

2393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0886

Hom.:

202

Bravo

AF:

0.0608

Asia WGS

AF:

0.0120

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leber congenital amaurosis 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.6

(source)

DANN

Benign

0.78

PhyloP100

-0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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14-88391362-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over