Genetic Variant SPATA17:p.Arg324Gln (chr1-217801816-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138796.4(SPATA17):c.971G>A(p.Arg324Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000549 in 1,458,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SPATA17
NM_138796.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Variant links:

Genes affected

SPATA17 (HGNC:25184): (spermatogenesis associated 17) Predicted to enable calmodulin binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPATA17 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28762424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA17	NM_138796.4 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 9 of 11	ENST00000366933.5	NP_620151.1	Q96L03
SPATA17	NM_001375655.1 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 9 of 11		NP_001362584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPATA17	ENST00000366933.5 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 9 of 11	1	NM_138796.4	ENSP00000355900.4	Q96L03
SPATA17	ENST00000471021.1 link	n.99G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
SPATA17	ENST00000492747.2 link	n.*48G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247486

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133850

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1458078

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.971G>A (p.R324Q) alteration is located in exon 9 (coding exon 9) of the SPATA17 gene. This alteration results from a G to A substitution at nucleotide position 971, causing the arginine (R) at amino acid position 324 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.64

M_CAP

Benign

0.019

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.67

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

REVEL

Benign

0.078

Sift

Benign

0.067

Sift4G

Benign

0.097

Polyphen

0.89

Vest4

0.44

MutPred

0.44

Loss of helix (P = 0.0104);

MVP

0.29

MPC

0.12

ClinPred

0.64

GERP RS

4.1

Varity_R

0.13

gMVP

0.64

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over