9-35043606-C-A

Variant names:

• chr9-35043606-C-A
• rs145316956
• NM_203299.4:c.977C>A

Variant summary

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

The NM_203299.4(SPATA31G1):​c.977C>A​(p.Thr326Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. T326S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPATA31G1 NM_203299.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 0 publications found

Genes affected

SPATA31G1 (HGNC:31418): (SPATA31 subfamily G member 1)

ENSG00000279608 (HGNC:):

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=0.09224054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203299.4. 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
	SPATA31G1	NM_203299.4	MANE Select	c.977C>A	p.Thr326Asn	missense	Exon 2 of 2	NP_976044.2	Q5VYM1-1
	SPATA31G1	NM_001040410.3		c.872C>A	p.Thr291Asn	missense	Exon 2 of 2	NP_001035500.1
	SPATA31G1	NM_001040412.3		c.833C>A	p.Thr278Asn	missense	Exon 3 of 3	NP_001035502.1	Q5VYM1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31G1	ENST00000312292.6	TSL:1 MANE Select	c.977C>A	p.Thr326Asn	missense	Exon 2 of 2	ENSP00000308279.5	Q5VYM1-1
	SPATA31G1	ENST00000421362.6	TSL:4	c.833C>A	p.Thr278Asn	missense	Exon 3 of 3	ENSP00000393683.2	Q5VYM1-2
	SPATA31G1	ENST00000354479.5	TSL:2	c.758C>A	p.Thr253Asn	missense	Exon 2 of 2	ENSP00000346472.5	Q5VYM1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.8
DANN	Benign	0.97
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.53
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.034
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.089	T
Polyphen		0.70	P
Vest4		0.14
MutPred		0.19		Loss of sheet (P = 7e-04)
MVP		0.014
MPC		0.016
ClinPred		0.29	T
GERP RS		-0.56
Varity_R		0.13
gMVP		0.076
Mutation Taster		=93/7	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: rs145316956; hg19: chr9-35043603;