1-48298778-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019073.4(SPATA6):c.1402A>G(p.Lys468Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

Genes affected

SPATA6 (HGNC:18309): (spermatogenesis associated 6) Predicted to enable myosin light chain binding activity. Predicted to be involved in motile cilium assembly and spermatogenesis. Predicted to be located in extracellular region. Predicted to be active in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.35169494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA6	NM_019073.4	c.1402A>G	p.Lys468Glu	missense_variant	13/13	ENST00000371847.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA6	ENST00000371847.8	c.1402A>G	p.Lys468Glu	missense_variant	13/13	1	NM_019073.4	P4
SPATA6	ENST00000371843.7	c.1354A>G	p.Lys452Glu	missense_variant	13/13	1		A1
SPATA6	ENST00000396199.7	c.1360A>G	p.Lys454Glu	missense_variant	12/12	2
SPATA6	ENST00000603831.5	c.*494A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461770 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.1402A>G (p.K468E) alteration is located in exon 13 (coding exon 13) of the SPATA6 gene. This alteration results from a A to G substitution at nucleotide position 1402, causing the lysine (K) at amino acid position 468 to be replaced by a glutamic acid (E). 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	0.22
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N;.;N
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.53	P;.;P
Vest4		0.59
MutPred		0.32		Loss of MoRF binding (P = 9e-04);.;.;
MVP		0.048
MPC		0.28
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-48764450;