rs17807673

Variant names:

• chr20-18532728-C-T
• rs17807673
• NM_006363.6:c.1298C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-18532728-C-T
• chr20-18532728-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006363.6(SEC23B):​c.1298C>T​(p.Pro433Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,611,526 control chromosomes in the GnomAD database, including 15,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P433R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.10 (1072 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14661 hom.)
• Consequence: SEC23B NM_006363.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 7.34
• Publications: 36 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002571702).
• BP6: Variant 20-18532728-C-T is Benign according to our data. Variant chr20-18532728-C-T is described in ClinVar as Benign. ClinVar VariationId is 95380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

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.1298C>T	p.Pro433Leu	missense	Exon 11 of 20	NP_006354.2
	SEC23B	NM_001172745.3		c.1298C>T	p.Pro433Leu	missense	Exon 11 of 20	NP_001166216.1	Q15437
	SEC23B	NM_032985.6		c.1298C>T	p.Pro433Leu	missense	Exon 11 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.1298C>T	p.Pro433Leu	missense	Exon 11 of 20	ENSP00000497473.1	Q15437
	SEC23B	ENST00000336714.8	TSL:1	c.1298C>T	p.Pro433Leu	missense	Exon 11 of 20	ENSP00000338844.3	Q15437
	SEC23B	ENST00000377465.6	TSL:1	c.1298C>T	p.Pro433Leu	missense	Exon 11 of 20	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15548 AN: 152066 Hom.: 1074 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.0890

GnomAD2 exomes AF: 0.114 AC: 28684 AN: 251392 AF XY: 0.118

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.0963

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.00196

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.136 AC: 198794 AN: 1459342 Hom.: 14661 Cov.: 31 AF XY: 0.135 AC XY: 98314 AN XY: 726116

African (AFR) AF: 0.0203 AC: 680 AN: 33454

American (AMR) AF: 0.0970 AC: 4337 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0595 AC: 1554 AN: 26122

East Asian (EAS) AF: 0.00202 AC: 80 AN: 39696

South Asian (SAS) AF: 0.0977 AC: 8424 AN: 86228

European-Finnish (FIN) AF: 0.182 AC: 9719 AN: 53402

Middle Eastern (MID) AF: 0.0744 AC: 429 AN: 5764

European-Non Finnish (NFE) AF: 0.150 AC: 166110 AN: 1109628

Other (OTH) AF: 0.124 AC: 7461 AN: 60326

GnomAD4 genome AF: 0.102 AC: 15544 AN: 152184 Hom.: 1072 Cov.: 32 AF XY: 0.104 AC XY: 7762 AN XY: 74384

African (AFR) AF: 0.0248 AC: 1032 AN: 41552

American (AMR) AF: 0.0936 AC: 1429 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5188

South Asian (SAS) AF: 0.0916 AC: 441 AN: 4816

European-Finnish (FIN) AF: 0.193 AC: 2044 AN: 10574

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10060 AN: 67998

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.125 Hom.: 2769

Bravo AF: 0.0907

TwinsUK AF: 0.145 AC: 536

ALSPAC AF: 0.156 AC: 603

ESP6500AA AF: 0.0302 AC: 133

ESP6500EA AF: 0.144 AC: 1235

ExAC AF: 0.112 AC: 13624

Asia WGS AF: 0.0410 AC: 141 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.135

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Congenital dyserythropoietic anemia, type II (1)
-	-	1	Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		7.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.013	D
Polyphen		0.50	P
Vest4		0.17
MPC		0.20
ClinPred		0.093	T
GERP RS		4.8
Varity_R		0.36
gMVP		0.43
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs17807673; hg19: chr20-18513372; COSMIC: COSV52719453;