rs164181

Variant names:

• chr1-162375301-G-A
• rs164181
• NM_182581.4:c.206C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 25 publications found

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]

ENSG00000254706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPATA46	NM_182581.4	c.206C>T	p.Ala69Val	missense_variant	Exon 2 of 3	ENST00000367935.10	NP_872387.2
SPATA46	XM_005245103.4	c.104-685C>T		intron_variant	Intron 1 of 1		XP_005245160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA46	ENST00000367935.10	c.206C>T	p.Ala69Val	missense_variant	Exon 2 of 3	1	NM_182581.4	ENSP00000356912.4
ENSG00000254706	ENST00000420220.1	c.-11-6590G>A		intron_variant	Intron 2 of 3	5		ENSP00000398035.1

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

GnomAD2 exomes AF: 0.982 AC: 246784 AN: 251412 AF XY: 0.985

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 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

African (AFR) AF: 0.814 AC: 27206 AN: 33424

American (AMR) AF: 0.987 AC: 44152 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 25145 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39695 AN: 39696

South Asian (SAS) AF: 0.993 AC: 85599 AN: 86238

European-Finnish (FIN) AF: 0.998 AC: 53329 AN: 53416

Middle Eastern (MID) AF: 0.965 AC: 5561 AN: 5762

European-Non Finnish (NFE) AF: 0.997 AC: 1107914 AN: 1111264

Other (OTH) AF: 0.980 AC: 59189 AN: 60370

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

African (AFR) AF: 0.821 AC: 34057 AN: 41500

American (AMR) AF: 0.977 AC: 14938 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3349 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.991 AC: 4773 AN: 4816

European-Finnish (FIN) AF: 0.999 AC: 10611 AN: 10626

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67795 AN: 68032

Other (OTH) AF: 0.958 AC: 2024 AN: 2112

Alfa AF: 0.982 Hom.: 197458

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
PhyloP100		-0.090
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs164181; hg19: chr1-162345091; COSMIC: COSV108205935; COSMIC: COSV108205935;