chr1-48359748-C-A

Variant names:

• chr1-48359748-C-A
• rs772275124
• NM_019073.4:c.932G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019073.4. 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
	SPATA6	NM_019073.4	MANE Select	c.932G>T	p.Arg311Ile	missense	Exon 10 of 13	NP_061946.1	Q9NWH7-1
	SPATA6	NM_001286239.2		c.890G>T	p.Arg297Ile	missense	Exon 9 of 12	NP_001273168.1	A8MU33
	SPATA6	NM_001286238.2		c.932G>T	p.Arg311Ile	missense	Exon 10 of 13	NP_001273167.1	Q9NWH7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA6	ENST00000371847.8	TSL:1 MANE Select	c.932G>T	p.Arg311Ile	missense	Exon 10 of 13	ENSP00000360913.3	Q9NWH7-1
	SPATA6	ENST00000371843.7	TSL:1	c.932G>T	p.Arg311Ile	missense	Exon 10 of 13	ENSP00000360909.3	Q9NWH7-2
	SPATA6	ENST00000396199.7	TSL:2	c.890G>T	p.Arg297Ile	missense	Exon 9 of 12	ENSP00000379502.4	A8MU33

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

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5504

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111472

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.11
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.0050	B
Vest4		0.22
MutPred		0.63		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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs772275124; hg19: chr1-48825420;