rs114796215

Variant names:

• chr14-88385724-C-T
• rs114796215
• NM_018418.5:c.-95C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_018418.5(SPATA7):​c.-95C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,296,006 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0048 (12 hom., cov: 34)
  • Exomes 𝑓: 0.00079 (5 hom.)
• Consequence: SPATA7 NM_018418.5 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.0200
• Publications: 3 publications found

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):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, 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

ENSG00000296360 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-88385724-C-T is Benign according to our data. Variant chr14-88385724-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 884672.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00484 (737/152332) while in subpopulation AFR AF = 0.0162 (675/41578). AF 95% confidence interval is 0.0152. There are 12 homozygotes in GnomAd4. There are 333 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018418.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA7	NM_018418.5	MANE Select	c.-95C>T		5_prime_UTR	Exon 1 of 12	NP_060888.2	Q9P0W8-1
	SPATA7	NM_001040428.4		c.-95C>T		5_prime_UTR	Exon 1 of 11	NP_001035518.1	Q9P0W8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA7	ENST00000393545.9	TSL:1 MANE Select	c.-95C>T		5_prime_UTR	Exon 1 of 12	ENSP00000377176.4	Q9P0W8-1
	SPATA7	ENST00000356583.9	TSL:1	c.-95C>T		5_prime_UTR	Exon 1 of 11	ENSP00000348991.5	Q9P0W8-2
	SPATA7	ENST00000556553.5	TSL:1	c.-95C>T		5_prime_UTR	Exon 2 of 12	ENSP00000451128.1	Q9P0W8-2

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 733 AN: 152214 Hom.: 12 Cov.: 34

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000794 AC: 908 AN: 1143674 Hom.: 5 Cov.: 16 AF XY: 0.000733 AC XY: 422 AN XY: 575976

African (AFR) AF: 0.0191 AC: 530 AN: 27718

American (AMR) AF: 0.00120 AC: 43 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00652 AC: 154 AN: 23630

East Asian (EAS) AF: 0.00 AC: 0 AN: 35848

South Asian (SAS) AF: 0.0000535 AC: 4 AN: 74836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47134

Middle Eastern (MID) AF: 0.00153 AC: 7 AN: 4568

European-Non Finnish (NFE) AF: 0.0000900 AC: 76 AN: 844250

Other (OTH) AF: 0.00188 AC: 94 AN: 49994

GnomAD4 genome AF: 0.00484 AC: 737 AN: 152332 Hom.: 12 Cov.: 34 AF XY: 0.00447 AC XY: 333 AN XY: 74496

African (AFR) AF: 0.0162 AC: 675 AN: 41578

American (AMR) AF: 0.00144 AC: 22 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68022

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00580

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 3 (1)
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.75
PhyloP100		0.020
PromoterAI		0.059	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs114796215; hg19: chr14-88852068;