1-48298889-A-T

Variant names:

• chr1-48298889-A-T
• rs748620425
• NM_019073.4:c.1291T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019073.4(SPATA6):​c.1291T>A​(p.Cys431Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,286 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018747807).

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.1291T>A	p.Cys431Ser	missense	Exon 13 of 13	NP_061946.1	Q9NWH7-1
	SPATA6	NM_001286239.2		c.1249T>A	p.Cys417Ser	missense	Exon 12 of 12	NP_001273168.1	A8MU33
	SPATA6	NM_001286238.2		c.1243T>A	p.Cys415Ser	missense	Exon 13 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.1291T>A	p.Cys431Ser	missense	Exon 13 of 13	ENSP00000360913.3	Q9NWH7-1
	SPATA6	ENST00000371843.7	TSL:1	c.1243T>A	p.Cys415Ser	missense	Exon 13 of 13	ENSP00000360909.3	Q9NWH7-2
	SPATA6	ENST00000396199.7	TSL:2	c.1249T>A	p.Cys417Ser	missense	Exon 12 of 12	ENSP00000379502.4	A8MU33

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249062 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460286 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726426

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111482

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.087
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.31
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.69	N
PhyloP100		1.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.036
Sift	Benign	0.45	T
Sift4G	Benign	0.57	T
Polyphen		0.0020	B
Vest4		0.024
MutPred		0.22		Gain of relative solvent accessibility (P = 0.005)
MVP		0.030
MPC		0.063
ClinPred		0.019	T
GERP RS		3.4
Varity_R		0.085
gMVP		0.065
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

dbSNP: rs748620425; hg19: chr1-48764561; COSMIC: COSV64061105;