1-162375301-G-C

Position:

• chr1-162375301-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182581.4(SPATA46):​c.206C>G​(p.Ala69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A69V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA46	NM_182581.4	c.206C>G	p.Ala69Gly	missense_variant	2/3	ENST00000367935.10
SPATA46	XM_005245103.4	c.104-685C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA46	ENST00000367935.10	c.206C>G	p.Ala69Gly	missense_variant	2/3	1	NM_182581.4	P1
SPATA46	ENST00000493255.1	c.*134-685C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461068 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 726954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.41
DANN	Benign	0.36
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.013
Sift	Benign	0.65	T
Sift4G	Benign	0.56	T
Polyphen		0.15	B
Vest4		0.031
MutPred		0.27		Loss of sheet (P = 0.0315);
MVP		0.055
MPC		0.026
ClinPred		0.037	T
GERP RS		1.3
Varity_R		0.023
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.31		Position offset: -11

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;