rs147410912

chr20-18535655-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS1

The NM_006363.6(SEC23B):c.1317G>T(p.Glu439Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,613,780 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: SEC23B NM_006363.6 missense, splice_region
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.00500

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012220919).
• BP6: Variant 20-18535655-G-T is Benign according to our data. Variant chr20-18535655-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 532197.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00158 (240/152280) while in subpopulation AFR AF= 0.00546 (227/41564). AF 95% confidence interval is 0.00488. There are 1 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23B	NM_006363.6	c.1317G>T	p.Glu439Asp	missense_variant, splice_region_variant	12/20	ENST00000650089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000650089.1	c.1317G>T	p.Glu439Asp	missense_variant, splice_region_variant	12/20		NM_006363.6	P1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000453 AC: 114 AN: 251434 Hom.: 0 AF XY: 0.000302 AC XY: 41 AN XY: 135894

Gnomad AFR exome AF: 0.00597

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000174 AC: 255 AN: 1461500 Hom.: 3 Cov.: 30 AF XY: 0.000161 AC XY: 117 AN XY: 727084

Gnomad4 AFR exome AF: 0.00616

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000447

GnomAD4 genome AF: 0.00158 AC: 240 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00148 AC XY: 110 AN XY: 74456

Gnomad4 AFR AF: 0.00546

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000978 Hom.: 0

Bravo AF: 0.00191

ESP6500AA AF: 0.00567 AC: 25

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000486 AC: 59

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 03, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 03, 2022	- -

Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.030
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.088	T;T;T;.;T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.80
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.012	T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.5	M;M;M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.3	N;N;N;.;.;N
REVEL	Uncertain	0.51
Sift	Benign	0.076	T;T;T;.;.;T
Sift4G	Benign	0.18	T;T;T;.;.;T
Polyphen		0.0010	B;B;B;.;B;B
Vest4		0.70
MutPred		0.50		Loss of disorder (P = 0.1294);Loss of disorder (P = 0.1294);Loss of disorder (P = 0.1294);.;Loss of disorder (P = 0.1294);Loss of disorder (P = 0.1294);
MVP		0.76
MPC		0.21
ClinPred		0.038	T
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs147410912; hg19: chr20-18516299;