5-134661299-C-T

Variant names:

• chr5-134661299-C-T
• rs367589110
• NM_021982.3:c.278C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021982.3(SEC24A):​c.278C>T​(p.Ser93Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S93C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC24A NM_021982.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25873035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021982.3. 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
	SEC24A	NM_021982.3	MANE Select	c.278C>T	p.Ser93Phe	missense	Exon 2 of 23	NP_068817.1	O95486-1
	SEC24A	NM_001252231.2		c.278C>T	p.Ser93Phe	missense	Exon 2 of 13	NP_001239160.1	O95486-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24A	ENST00000398844.7	TSL:2 MANE Select	c.278C>T	p.Ser93Phe	missense	Exon 2 of 23	ENSP00000381823.2	O95486-1
	SEC24A	ENST00000322887.8	TSL:1	c.278C>T	p.Ser93Phe	missense	Exon 2 of 13	ENSP00000321749.4	O95486-2
	SEC24A	ENST00000903398.1		c.278C>T	p.Ser93Phe	missense	Exon 2 of 24	ENSP00000573457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.017	D
Polyphen		0.74	P
Vest4		0.37
MutPred		0.23		Loss of glycosylation at S93 (P = 0.0065)
MVP		0.94
MPC		0.18
ClinPred		0.66	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.28
Mutation Taster		=84/16	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: rs367589110; hg19: chr5-133996989;