9-35045566-C-A

Variant names:

• chr9-35045566-C-A
• rs1394906030
• NM_203299.4:c.2937C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_203299.4(SPATA31G1):​c.2937C>A​(p.Ser979Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SPATA31G1 NM_203299.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.309

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019129425).
• BP6: Variant 9-35045566-C-A is Benign according to our data. Variant chr9-35045566-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2237994.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31G1	NM_203299.4	c.2937C>A	p.Ser979Arg	missense_variant	Exon 2 of 2	ENST00000312292.6	NP_976044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9orf131	ENST00000312292.6	c.2937C>A	p.Ser979Arg	missense_variant	Exon 2 of 2	1	NM_203299.4	ENSP00000308279.5
C9orf131	ENST00000421362.6	c.2793C>A	p.Ser931Arg	missense_variant	Exon 3 of 3	4		ENSP00000393683.2
C9orf131	ENST00000354479.5	c.2718C>A	p.Ser906Arg	missense_variant	Exon 2 of 2	2		ENSP00000346472.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461878 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727242

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: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 15, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.18
DANN	Benign	0.59
DEOGEN2	Benign	0.0014	.;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.019	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.1	.;.;N
PROVEAN	Benign	2.8	N;N;N
REVEL	Benign	0.023
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.085
MutPred		0.20		.;.;Gain of MoRF binding (P = 0.0172);
MVP		0.014
MPC		0.012
ClinPred		0.094	T
GERP RS		-1.7
Varity_R		0.045
gMVP		0.070

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

Publications

LitVar

Other links and lift over

dbSNP: rs1394906030; hg19: chr9-35045563;