chr4-82842234-T-C

Variant names:

• chr4-82842234-T-C
• rs771768482
• NM_001077207.4:c.2874A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001077207.4(SEC31A):​c.2874A>G​(p.Pro958Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SEC31A NM_001077207.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.580
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.075).
• BP6: Variant 4-82842234-T-C is Benign according to our data. Variant chr4-82842234-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2654847.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.58 with no splicing effect.

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.2874A>G	p.Pro958Pro	synonymous	Exon 22 of 27	NP_001070675.1	O94979-1
	SEC31A	NM_001400154.1		c.2967A>G	p.Pro989Pro	synonymous	Exon 23 of 28	NP_001387083.1	D6REX3
	SEC31A	NM_001400155.1		c.2967A>G	p.Pro989Pro	synonymous	Exon 23 of 28	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.2874A>G	p.Pro958Pro	synonymous	Exon 22 of 27	ENSP00000378721.2	O94979-1
	SEC31A	ENST00000508502.5	TSL:1	c.2874A>G	p.Pro958Pro	synonymous	Exon 22 of 27	ENSP00000424635.1	O94979-2
	SEC31A	ENST00000348405.8	TSL:1	c.2757A>G	p.Pro919Pro	synonymous	Exon 20 of 25	ENSP00000337602.5	O94979-4

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152098 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000180 AC: 45 AN: 250330 AF XY: 0.000274

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 173 AN: 1461266 Hom.: 0 Cov.: 31 AF XY: 0.000164 AC XY: 119 AN XY: 726876

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000671 AC: 3 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000951 AC: 82 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.0000639 AC: 71 AN: 1111608

Other (OTH) AF: 0.000199 AC: 12 AN: 60364

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152098 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000756

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.4
DANN	Benign	0.61
PhyloP100		0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs771768482; hg19: chr4-83763387;