rs36023150

Variant names:

• chr20-18524556-G-T
• rs36023150
• NM_006363.6:c.490G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-18524556-G-T
• chr20-18524556-G-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP3 BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006363.6(SEC23B):​c.490G>T​(p.Val164Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 1,614,174 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (13 hom., cov: 32)
  • Exomes 𝑓: 0.010 (149 hom.)
• Consequence: SEC23B NM_006363.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:6
• Conservation: PhyloP100: 8.12
• Publications: 21 publications found

Genes affected

SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

SEC23B Gene-Disease associations (from GenCC):

• congenital dyserythropoietic anemia type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P, PanelApp Australia, Laboratory for Molecular Medicine
• Cowden disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Cowden syndrome 7

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• congenital dyserythropoietic anemia

  Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.01537177).
• BP6: Variant 20-18524556-G-T is Benign according to our data. Variant chr20-18524556-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00769 (1171/152296) while in subpopulation SAS AF = 0.0358 (173/4828). AF 95% confidence interval is 0.0315. There are 13 homozygotes in GnomAd4. There are 590 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006363.6. 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
	SEC23B	NM_006363.6	MANE Select	c.490G>T	p.Val164Leu	missense	Exon 5 of 20	NP_006354.2
	SEC23B	NM_001172745.3		c.490G>T	p.Val164Leu	missense	Exon 5 of 20	NP_001166216.1	Q15437
	SEC23B	NM_032985.6		c.490G>T	p.Val164Leu	missense	Exon 5 of 20	NP_116780.1	Q15437

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23B	ENST00000650089.1	MANE Select	c.490G>T	p.Val164Leu	missense	Exon 5 of 20	ENSP00000497473.1	Q15437
	SEC23B	ENST00000336714.8	TSL:1	c.490G>T	p.Val164Leu	missense	Exon 5 of 20	ENSP00000338844.3	Q15437
	SEC23B	ENST00000377465.6	TSL:1	c.490G>T	p.Val164Leu	missense	Exon 5 of 20	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes AF: 0.00770 AC: 1172 AN: 152178 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.0108 AC: 2716 AN: 251424 AF XY: 0.0124

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.0191

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00665

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0121

GnomAD4 exome AF: 0.0102 AC: 14864 AN: 1461878 Hom.: 149 Cov.: 32 AF XY: 0.0110 AC XY: 8023 AN XY: 727244

African (AFR) AF: 0.00122 AC: 41 AN: 33480

American (AMR) AF: 0.00494 AC: 221 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 515 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0311 AC: 2685 AN: 86256

European-Finnish (FIN) AF: 0.00696 AC: 372 AN: 53418

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.00935 AC: 10392 AN: 1112000

Other (OTH) AF: 0.00945 AC: 571 AN: 60396

GnomAD4 genome AF: 0.00769 AC: 1171 AN: 152296 Hom.: 13 Cov.: 32 AF XY: 0.00792 AC XY: 590 AN XY: 74466

African (AFR) AF: 0.00159 AC: 66 AN: 41556

American (AMR) AF: 0.00601 AC: 92 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0358 AC: 173 AN: 4828

European-Finnish (FIN) AF: 0.00537 AC: 57 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 716 AN: 68028

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00891 Hom.: 25

Bravo AF: 0.00726

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.00988 AC: 85

ExAC AF: 0.0118 AC: 1432

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.0115

EpiControl AF: 0.0107

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital dyserythropoietic anemia, type II (1)
-	-	1	Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 (1)
-	1	-	Cowden syndrome 7 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		8.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.87	P
Vest4		0.71
MutPred		0.69		Loss of sheet (P = 0.0104)
MPC		0.62
ClinPred		0.055	T
GERP RS		4.9
Varity_R		0.69
gMVP		0.63
Mutation Taster		=97/3	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: rs36023150; hg19: chr20-18505200; COSMIC: COSV52721902;