3-10301335-A-G

Variant names:

• chr3-10301335-A-G
• NM_183352.3:c.895T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_183352.3(SEC13):​c.895T>C​(p.Cys299Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SEC13 NM_183352.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.18

Genes affected

SEC13 (HGNC:10697): (SEC13 homolog, nuclear pore and COPII coat complex component) The protein encoded by this gene belongs to the SEC13 family of WD-repeat proteins. It is a constituent of the endoplasmic reticulum and the nuclear pore complex. It has similarity to the yeast SEC13 protein, which is required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC13	NM_183352.3	c.895T>C	p.Cys299Arg	missense_variant	Exon 9 of 9	ENST00000350697.8	NP_899195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC13	ENST00000350697.8	c.895T>C	p.Cys299Arg	missense_variant	Exon 9 of 9	1	NM_183352.3	ENSP00000312122.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;.;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.2	.;.;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.6	D;D;D;D
REVEL	Uncertain	0.63
Sift	Benign	0.57	T;T;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.87	.;.;P;.
Vest4		0.86
MutPred		0.58		.;.;Gain of MoRF binding (P = 0.0029);.;
MVP		0.89
MPC		0.44
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.93
gMVP		0.80

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: chr3-10343019;