rs3179969

chr14-88396185-G-Achr14-88396185-G-Cchr14-88396185-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018418.5(SPATA7):c.220G>A(p.Val74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,604,060 control chromosomes in the GnomAD database, including 98,114 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12205 hom., cov: 32)
  • Exomes 𝑓: 0.34 (85909 hom.)
• Consequence: SPATA7 NM_018418.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.07

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2908449E-5).
• BP6: Variant 14-88396185-G-A is Benign according to our data. Variant chr14-88396185-G-A is described in ClinVar as [Benign]. Clinvar id is 286866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-88396185-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA7	NM_018418.5	c.220G>A	p.Val74Met	missense_variant	4/12	ENST00000393545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA7	ENST00000393545.9	c.220G>A	p.Val74Met	missense_variant	4/12	1	NM_018418.5	P2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58689 AN: 151648 Hom.: 12175 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.337 AC: 84495 AN: 250882 Hom.: 14984 AF XY: 0.337 AC XY: 45648 AN XY: 135624

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.234

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.320

Gnomad SAS exome AF: 0.396

Gnomad FIN exome AF: 0.280

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.339 AC: 492221 AN: 1452296 Hom.: 85909 Cov.: 31 AF XY: 0.340 AC XY: 245935 AN XY: 722918

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.387 AC: 58790 AN: 151764 Hom.: 12205 Cov.: 32 AF XY: 0.380 AC XY: 28204 AN XY: 74136

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.347

Alfa AF: 0.339 Hom.: 21196

Bravo AF: 0.391

TwinsUK AF: 0.330 AC: 1225

ALSPAC AF: 0.338 AC: 1302

ESP6500AA AF: 0.544 AC: 2396

ESP6500EA AF: 0.343 AC: 2948

ExAC AF: 0.346 AC: 42053

Asia WGS AF: 0.387 AC: 1346 AN: 3476

EpiCase AF: 0.329

EpiControl AF: 0.325

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leber congenital amaurosis 3 Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 04, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	16
Dann	Benign	0.87
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.046	N
MetaRNN	Benign	0.000023	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.1	N;N;N;N;N;N
REVEL	Benign	0.067
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0010	B;B;B;.;.;.
Vest4		0.11
MPC		0.095
ClinPred		0.0065	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.020
gMVP		0.041

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3179969; hg19: chr14-88862529; COSMIC: COSV50420576; COSMIC: COSV50420576;