rs756779840

Variant names:

• chr1-48399425-G-A
• rs756779840
• NM_019073.4:c.706C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019073.4(SPATA6):​c.706C>T​(p.Arg236Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,613,036 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: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22495404).

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.706C>T	p.Arg236Trp	missense	Exon 7 of 13	NP_061946.1	Q9NWH7-1
	SPATA6	NM_001286239.2		c.664C>T	p.Arg222Trp	missense	Exon 6 of 12	NP_001273168.1	A8MU33
	SPATA6	NM_001286238.2		c.706C>T	p.Arg236Trp	missense	Exon 7 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.706C>T	p.Arg236Trp	missense	Exon 7 of 13	ENSP00000360913.3	Q9NWH7-1
	SPATA6	ENST00000371843.7	TSL:1	c.706C>T	p.Arg236Trp	missense	Exon 7 of 13	ENSP00000360909.3	Q9NWH7-2
	SPATA6	ENST00000396199.7	TSL:2	c.664C>T	p.Arg222Trp	missense	Exon 6 of 12	ENSP00000379502.4	A8MU33

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151874 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251014 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000876 AC: 128 AN: 1461162 Hom.: 0 Cov.: 30 AF XY: 0.0000949 AC XY: 69 AN XY: 726890

African (AFR) AF: 0.0000299 AC: 1 AN: 33444

American (AMR) AF: 0.0000448 AC: 2 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39682

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.0000927 AC: 103 AN: 1111558

Other (OTH) AF: 0.0000663 AC: 4 AN: 60350

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151874 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74188

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67884

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.38		Loss of disorder (P = 0.0076)
MVP		0.64
MPC		0.35
ClinPred		0.20	T
GERP RS		4.8
Varity_R		0.37
gMVP		0.43
Mutation Taster		=77/23	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: rs756779840; hg19: chr1-48865097; COSMIC: COSV64056967; COSMIC: COSV64056967;