chr14-88426674-GG-TC

Variant names:

• chr14-88426674-GG-TC
• NM_018418.5:c.815_816delGGinsTC
• SPATA7 p.Arg272Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018418.5(SPATA7):​c.815_816delGGinsTC​(p.Arg272Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R272Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA7 NM_018418.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.815_816delGGinsTC	p.Arg272Leu	missense	N/A	NP_060888.2	Q9P0W8-1
	SPATA7	NM_001040428.4		c.719_720delGGinsTC	p.Arg240Leu	missense	N/A	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.815_816delGGinsTC	p.Arg272Leu	missense	N/A	ENSP00000377176.4	Q9P0W8-1
	SPATA7	ENST00000356583.9	TSL:1	c.719_720delGGinsTC	p.Arg240Leu	missense	N/A	ENSP00000348991.5	Q9P0W8-2
	SPATA7	ENST00000556553.5	TSL:1	c.719_720delGGinsTC	p.Arg240Leu	missense	N/A	ENSP00000451128.1	Q9P0W8-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-88893018;