rs4572871

Variant names:

• chr4-82839734-A-G
• rs4572871
• NM_001077207.4:c.2968+2406T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077207.4(SEC31A):​c.2968+2406T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,174 control chromosomes in the GnomAD database, including 35,930 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (35930 hom., cov: 33)
• Consequence: SEC31A NM_001077207.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 11 publications found

Genes affected

SEC31A (HGNC:17052): (SEC31 homolog A, COPII coat complex component) The protein encoded by this gene shares similarity with the yeast Sec31 protein, and is a component of the outer layer of the coat protein complex II (COPII). The encoded protein is involved in vesicle budding from the endoplasmic reticulum (ER) and contains multiple WD repeats near the N-terminus and a proline-rich region in the C-terminal half. It associates with the protein encoded by the SEC13 homolog, nuclear pore and COPII coat complex component (SEC13), and is required for ER-Golgi transport. Monoubiquitylation of this protein by CUL3-KLHL12 was found to regulate the size of COPII coats to accommodate unusually shaped cargo. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC31A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077207.4. 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
	SEC31A	NM_001077207.4	MANE Select	c.2968+2406T>C		intron	N/A	NP_001070675.1	O94979-1
	SEC31A	NM_001400154.1		c.3061+2406T>C		intron	N/A	NP_001387083.1	D6REX3
	SEC31A	NM_001400155.1		c.3061+2406T>C		intron	N/A	NP_001387084.1	D6REX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC31A	ENST00000395310.7	TSL:1 MANE Select	c.2968+2406T>C		intron	N/A	ENSP00000378721.2	O94979-1
	SEC31A	ENST00000508502.5	TSL:1	c.2923+2451T>C		intron	N/A	ENSP00000424635.1	O94979-2
	SEC31A	ENST00000348405.8	TSL:1	c.2851+2406T>C		intron	N/A	ENSP00000337602.5	O94979-4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100456 AN: 152056 Hom.: 35920 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.705

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.660 AC: 100495 AN: 152174 Hom.: 35930 Cov.: 33 AF XY: 0.661 AC XY: 49158 AN XY: 74374

African (AFR) AF: 0.369 AC: 15324 AN: 41518

American (AMR) AF: 0.779 AC: 11913 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2717 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2651 AN: 5174

South Asian (SAS) AF: 0.698 AC: 3370 AN: 4828

European-Finnish (FIN) AF: 0.765 AC: 8093 AN: 10574

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53927 AN: 68004

Other (OTH) AF: 0.707 AC: 1491 AN: 2110

Alfa AF: 0.713 Hom.: 8047

Bravo AF: 0.650

Asia WGS AF: 0.632 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs4572871; hg19: chr4-83760887;