5-134661373-A-G

Variant names:

• chr5-134661373-A-G
• rs745680774
• NM_021982.3:c.352A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021982.3(SEC24A):​c.352A>G​(p.Thr118Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. T118P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SEC24A NM_021982.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030273825).

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.352A>G	p.Thr118Ala	missense	Exon 2 of 23	NP_068817.1	O95486-1
	SEC24A	NM_001252231.2		c.352A>G	p.Thr118Ala	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.352A>G	p.Thr118Ala	missense	Exon 2 of 23	ENSP00000381823.2	O95486-1
	SEC24A	ENST00000322887.8	TSL:1	c.352A>G	p.Thr118Ala	missense	Exon 2 of 13	ENSP00000321749.4	O95486-2
	SEC24A	ENST00000903398.1		c.352A>G	p.Thr118Ala	missense	Exon 2 of 24	ENSP00000573457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249574 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.6
DANN	Benign	0.11
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	-1.5	N
PhyloP100		1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.14		Loss of glycosylation at T118 (P = 0.0016)
MVP		0.59
MPC		0.097
ClinPred		0.0091	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.13
Mutation Taster		=98/2	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: rs745680774; hg19: chr5-133997063;