rs164181

Positions:

• chr1-162375301-G-A
• chr1-162375301-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182581.4(SPATA46):​c.206C>T​(p.Ala69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,613,244 control chromosomes in the GnomAD database, including 786,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.95 (68515 hom., cov: 31)
  • Exomes 𝑓: 0.99 (717951 hom.)
• Consequence: SPATA46 NM_182581.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

SPATA46 (HGNC:27648): (spermatogenesis associated 46) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization and spermatogenesis. Predicted to be active in nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.8746947E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA46	NM_182581.4	c.206C>T	p.Ala69Val	missense_variant	2/3	ENST00000367935.10
SPATA46	XM_005245103.4	c.104-685C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA46	ENST00000367935.10	c.206C>T	p.Ala69Val	missense_variant	2/3	1	NM_182581.4	P1
SPATA46	ENST00000493255.1	c.*134-685C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143820 AN: 152112 Hom.: 68477 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.958

GnomAD3 exomes AF: 0.982 AC: 246784 AN: 251412 Hom.: 121390 AF XY: 0.985 AC XY: 133832 AN XY: 135862

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.962

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.992

Gnomad FIN exome AF: 0.998

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.985

GnomAD4 exome AF: 0.991 AC: 1447790 AN: 1461014 Hom.: 717951 Cov.: 40 AF XY: 0.991 AC XY: 720702 AN XY: 726934

Gnomad4 AFR exome AF: 0.814

Gnomad4 AMR exome AF: 0.987

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.993

Gnomad4 FIN exome AF: 0.998

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.980

GnomAD4 genome AF: 0.945 AC: 143915 AN: 152230 Hom.: 68515 Cov.: 31 AF XY: 0.947 AC XY: 70498 AN XY: 74438

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.958

Alfa AF: 0.984 Hom.: 147923

Bravo AF: 0.937

TwinsUK AF: 0.997 AC: 3696

ALSPAC AF: 0.997 AC: 3843

ESP6500AA AF: 0.817 AC: 3598

ESP6500EA AF: 0.996 AC: 8567

ExAC AF: 0.979 AC: 118843

Asia WGS AF: 0.986 AC: 3428 AN: 3478

EpiCase AF: 0.995

EpiControl AF: 0.994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.046
DANN	Benign	0.35
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00046	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	0.070	N
REVEL	Benign	0.021
Sift	Benign	0.93	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.026
ClinPred		0.00011	T
GERP RS		1.3
Varity_R		0.016
gMVP		0.050

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs164181; hg19: chr1-162345091;