chr1-48359763-C-T

Variant names:

• chr1-48359763-C-T
• NM_019073.4:c.917G>A

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.917G>A​(p.Arg306Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• 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=0.122332454).

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.917G>A	p.Arg306Lys	missense	Exon 10 of 13	NP_061946.1	Q9NWH7-1
	SPATA6	NM_001286239.2		c.875G>A	p.Arg292Lys	missense	Exon 9 of 12	NP_001273168.1	A8MU33
	SPATA6	NM_001286238.2		c.917G>A	p.Arg306Lys	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.917G>A	p.Arg306Lys	missense	Exon 10 of 13	ENSP00000360913.3	Q9NWH7-1
	SPATA6	ENST00000371843.7	TSL:1	c.917G>A	p.Arg306Lys	missense	Exon 10 of 13	ENSP00000360909.3	Q9NWH7-2
	SPATA6	ENST00000396199.7	TSL:2	c.875G>A	p.Arg292Lys	missense	Exon 9 of 12	ENSP00000379502.4	A8MU33

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.047
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N
PhyloP100		2.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.021
Sift	Benign	0.14	T
Sift4G	Benign	0.38	T
Polyphen		0.0020	B
Vest4		0.081
MutPred		0.36		Gain of methylation at R306 (P = 0.0062)
MVP		0.28
MPC		0.32
ClinPred		0.50	D
GERP RS		4.1
Varity_R		0.18
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr1-48825435;