9-35043606-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_203299.4(SPATA31G1):​c.977C>G​(p.Thr326Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,614,088 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SPATA31G1 NM_203299.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.530
• Publications: 3 publications found

Genes affected

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

ENSG00000279608 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07189405).

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>G	p.Thr326Ser	missense	Exon 2 of 2	NP_976044.2	Q5VYM1-1
	SPATA31G1	NM_001040410.3		c.872C>G	p.Thr291Ser	missense	Exon 2 of 2	NP_001035500.1
	SPATA31G1	NM_001040412.3		c.833C>G	p.Thr278Ser	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>G	p.Thr326Ser	missense	Exon 2 of 2	ENSP00000308279.5	Q5VYM1-1
	SPATA31G1	ENST00000421362.6	TSL:4	c.833C>G	p.Thr278Ser	missense	Exon 3 of 3	ENSP00000393683.2	Q5VYM1-2
	SPATA31G1	ENST00000354479.5	TSL:2	c.758C>G	p.Thr253Ser	missense	Exon 2 of 2	ENSP00000346472.5	Q5VYM1-3

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251416 AF XY: 0.0000883

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000205 AC: 299 AN: 1461880 Hom.: 0 Cov.: 36 AF XY: 0.000184 AC XY: 134 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 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: 0.000248 AC: 276 AN: 1112004

Other (OTH) AF: 0.000315 AC: 19 AN: 60396

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000249 Hom.: 0

Bravo AF: 0.000174

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.1
DANN	Benign	0.95
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.53
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.042
Sift	Uncertain	0.018	D
Sift4G	Benign	0.56	T
Polyphen		0.87	P
Vest4		0.098
MutPred		0.15		Loss of sheet (P = 7e-04)
MVP		0.030
MPC		0.056
ClinPred		0.031	T
GERP RS		-0.56
Varity_R		0.070
gMVP		0.069
Mutation Taster		=98/2	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;