chr1-48298760-A-G

Variant names:

• chr1-48298760-A-G
• rs1459444392
• NM_019073.4:c.1420T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019073.4(SPATA6):​c.1420T>C​(p.Tyr474His) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y474N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1420T>C	p.Tyr474His	missense	Exon 13 of 13	NP_061946.1	Q9NWH7-1
	SPATA6	NM_001286239.2		c.1378T>C	p.Tyr460His	missense	Exon 12 of 12	NP_001273168.1	A8MU33
	SPATA6	NM_001286238.2		c.1372T>C	p.Tyr458His	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.1420T>C	p.Tyr474His	missense	Exon 13 of 13	ENSP00000360913.3	Q9NWH7-1
	SPATA6	ENST00000371843.7	TSL:1	c.1372T>C	p.Tyr458His	missense	Exon 13 of 13	ENSP00000360909.3	Q9NWH7-2
	SPATA6	ENST00000396199.7	TSL:2	c.1378T>C	p.Tyr460His	missense	Exon 12 of 12	ENSP00000379502.4	A8MU33

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461646 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111874

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.49		Loss of stability (P = 0.02)
MVP		0.18
MPC		0.38
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.41
Mutation Taster		=90/10	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: rs1459444392; hg19: chr1-48764432;