2-230996495-G-C

Variant names:

• chr2-230996495-G-C
• rs149976648
• NM_139073.5:c.262G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139073.5(SPATA3):​c.262G>C​(p.Asp88His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. D88N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 8 publications found

Genes affected

SPATA3 (HGNC:17884): (spermatogenesis associated 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA3 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118180364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5	c.262G>C	p.Asp88His	missense_variant	Exon 1 of 5	ENST00000433428.7	NP_620712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA3	ENST00000433428.7	c.262G>C	p.Asp88His	missense_variant	Exon 1 of 5	1	NM_139073.5	ENSP00000403804.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1399858 Hom.: 0 Cov.: 34 AF XY: 0.00000724 AC XY: 5 AN XY: 690404

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000649 AC: 7 AN: 1079066

Other (OTH) AF: 0.00 AC: 0 AN: 58140

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.8
DANN	Benign	0.42
DEOGEN2	Benign	0.036	T;T;T;.;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.35	.;.;.;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;L;L;.;L;.
PhyloP100		-0.40
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;N;N;.;N;D
REVEL	Benign	0.095
Sift	Benign	0.036	D;D;D;.;D;.
Sift4G	Uncertain	0.013	D;D;D;D;D;D
Vest4		0.14
MVP		0.048
ClinPred		0.38	T
GERP RS		-1.8
PromoterAI		-0.014	Neutral
Varity_R		0.059
gMVP		0.049
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149976648; hg19: chr2-231861210;