NM_021982.3:c.2266+30G>A

Variant names:

• chr5-134698087-G-A
• rs246341
• NM_021982.3:c.2266+30G>A

Variant summary

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

The NM_021982.3(SEC24A):​c.2266+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,572,916 control chromosomes in the GnomAD database, including 739,538 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 0.98 (72844 hom., cov: 29)
  • Exomes 𝑓: 0.97 (666694 hom.)
• Consequence: SEC24A NM_021982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24A	NM_021982.3	MANE Select	c.2266+30G>A		intron	N/A	NP_068817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24A	ENST00000398844.7	TSL:2 MANE Select	c.2266+30G>A		intron	N/A	ENSP00000381823.2

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148730 AN: 152030 Hom.: 72781 Cov.: 29

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.983

GnomAD2 exomes AF: 0.977 AC: 220095 AN: 225330 AF XY: 0.976

Gnomad AFR exome AF: 0.994

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.974

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.975

Gnomad NFE exome AF: 0.967

Gnomad OTH exome AF: 0.978

GnomAD4 exome AF: 0.969 AC: 1376251 AN: 1420768 Hom.: 666694 Cov.: 23 AF XY: 0.969 AC XY: 685581 AN XY: 707524

African (AFR) AF: 0.995 AC: 31561 AN: 31710

American (AMR) AF: 0.990 AC: 37849 AN: 38246

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 24266 AN: 24906

East Asian (EAS) AF: 1.00 AC: 39465 AN: 39468

South Asian (SAS) AF: 0.981 AC: 79417 AN: 80994

European-Finnish (FIN) AF: 0.977 AC: 49950 AN: 51148

Middle Eastern (MID) AF: 0.978 AC: 5468 AN: 5590

European-Non Finnish (NFE) AF: 0.964 AC: 1051049 AN: 1089822

Other (OTH) AF: 0.972 AC: 57226 AN: 58884

GnomAD4 genome AF: 0.978 AC: 148852 AN: 152148 Hom.: 72844 Cov.: 29 AF XY: 0.979 AC XY: 72803 AN XY: 74376

African (AFR) AF: 0.994 AC: 41258 AN: 41526

American (AMR) AF: 0.990 AC: 15076 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3377 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.982 AC: 4743 AN: 4830

European-Finnish (FIN) AF: 0.973 AC: 10298 AN: 10586

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65653 AN: 68012

Other (OTH) AF: 0.983 AC: 2076 AN: 2112

Alfa AF: 0.970 Hom.: 35257

Bravo AF: 0.980

Asia WGS AF: 0.991 AC: 3447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.74
PhyloP100		0.40
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: rs246341; hg19: chr5-134033777;