5-134661491-C-T

Variant names:

• chr5-134661491-C-T
• NM_021982.3:c.470C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021982.3(SEC24A):​c.470C>T​(p.Ser157Phe) 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 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SEC24A NM_021982.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

SEC24A (HGNC:10703): (SEC24 homolog A, COPII coat complex component) The protein encoded by this gene belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

LOC124901192 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23750237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24A	NM_021982.3	c.470C>T	p.Ser157Phe	missense_variant	Exon 2 of 23	ENST00000398844.7	NP_068817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24A	ENST00000398844.7	c.470C>T	p.Ser157Phe	missense_variant	Exon 2 of 23	2	NM_021982.3	ENSP00000381823.2
SEC24A	ENST00000322887.8	c.470C>T	p.Ser157Phe	missense_variant	Exon 2 of 13	1		ENSP00000321749.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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	Benign	0.089
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	0.0031
Eigen_PC	Benign	0.020
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.29
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.18	T;D
Polyphen		0.61	P;.
Vest4		0.35
MutPred		0.35		Loss of glycosylation at S157 (P = 0.0227);Loss of glycosylation at S157 (P = 0.0227);
MVP		0.92
MPC		0.21
ClinPred		0.56	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.26

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: chr5-133997181;