chr1-48359748-C-A

Variant names:

• chr1-48359748-C-A
• NM_019073.4:c.932G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019073.4(SPATA6):​c.932G>T​(p.Arg311Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. R311K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2428836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA6	NM_019073.4	c.932G>T	p.Arg311Ile	missense_variant	Exon 10 of 13	ENST00000371847.8	NP_061946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA6	ENST00000371847.8	c.932G>T	p.Arg311Ile	missense_variant	Exon 10 of 13	1	NM_019073.4	ENSP00000360913.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460532 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726548

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T;T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.46	N;.;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N;.;N;D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;.
Polyphen		0.0050	B;.;B;.
Vest4		0.22
MutPred		0.63		Loss of disorder (P = 0.0382);.;Loss of disorder (P = 0.0382);.;
MVP		0.18
MPC		0.44
ClinPred		0.59	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr1-48825420;