9-35043671-G-C

Position:

• chr9-35043671-G-C

Variant summary

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

The ENST00000312292.6(C9orf131):​c.1042G>C​(p.Ala348Pro) 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 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C9orf131 ENST00000312292.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.383

Genes affected

C9orf131 (HGNC:31418): (SPATA31 subfamily G member 1)

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05849737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C9orf131	NM_203299.4	c.1042G>C	p.Ala348Pro	missense_variant	2/2	ENST00000312292.6	NP_976044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C9orf131	ENST00000312292.6	c.1042G>C	p.Ala348Pro	missense_variant	2/2	1	NM_203299.4	ENSP00000308279	P2
	ENST00000624351.1	n.656C>G		non_coding_transcript_exon_variant	1/1
C9orf131	ENST00000421362.6	c.898G>C	p.Ala300Pro	missense_variant	3/3	4		ENSP00000393683	A2
C9orf131	ENST00000354479.5	c.823G>C	p.Ala275Pro	missense_variant	2/2	2		ENSP00000346472	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.1042G>C (p.A348P) alteration is located in exon 2 (coding exon 2) of the C9orf131 gene. This alteration results from a G to C substitution at nucleotide position 1042, causing the alanine (A) at amino acid position 348 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	.;.;L
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.021	.;.;B
Vest4		0.084
MutPred		0.13		.;.;Gain of relative solvent accessibility (P = 0.0023);
MVP		0.048
MPC		0.028
ClinPred		0.056	T
GERP RS		-2.3
Varity_R		0.10
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35043668;