Variant 10-119919501-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007190.4(SEC23IP):c.1930A>G(p.Lys644Glu) variant causes a missense change. The variant allele was found at a frequency of 0.683 in 1,612,424 control chromosomes in the GnomAD database, including 377,922 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.71 ( 38845 hom., cov: 31)

Exomes 𝑓: 0.68 ( 339077 hom. )

Consequence

SEC23IP
NM_007190.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

SEC23IP (HGNC:17018): (SEC23 interacting protein) This gene encodes a member of the phosphatidic acid preferring-phospholipase A1 family. The encoded protein is localized to endoplasmic reticulum exit sites and plays a critical role in ER-Golgi transport as part of the multimeric coat protein II complex. An orthologous gene in frogs is required for normal neural crest cell development, suggesting that this gene may play a role in Waardenburg syndrome neural crest defects. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

SEC23IP links:

SEC23IP (HGNC:):

SEC23IP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.4852725E-7).

BP6

Variant 10-119919501-A-G is Benign according to our data. Variant chr10-119919501-A-G is described in ClinVar as [Benign]. Clinvar id is 3059313.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23IP	NM_007190.4 linkuse as main transcript	c.1930A>G	p.Lys644Glu	missense_variant	11/19	ENST00000369075.8	NP_009121.1	Q9Y6Y8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8 linkuse as main transcript	c.1930A>G	p.Lys644Glu	missense_variant	11/19	1	NM_007190.4	ENSP00000358071.3		Q9Y6Y8-1
SEC23IP	ENST00000705471.1 linkuse as main transcript	c.1930A>G	p.Lys644Glu	missense_variant	11/19			ENSP00000516127.1		A0A994J542

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108193

AN:

151890

Hom.:

38798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.701

GnomAD3 exomes

AF:

0.715

AC:

179039

AN:

250552

Hom.:

64378

AF XY:

0.713

AC XY:

96557

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.784

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.725

Gnomad EAS exome

AF:

0.825

Gnomad SAS exome

AF:

0.744

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.680

AC:

992523

AN:

1460416

Hom.:

339077

Cov.:

AF XY:

0.682

AC XY:

495472

AN XY:

726536

show subpopulations

Gnomad4 AFR exome

AF:

0.785

Gnomad4 AMR exome

AF:

0.757

Gnomad4 ASJ exome

AF:

0.718

Gnomad4 EAS exome

AF:

0.830

Gnomad4 SAS exome

AF:

0.743

Gnomad4 FIN exome

AF:

0.652

Gnomad4 NFE exome

AF:

0.663

Gnomad4 OTH exome

AF:

0.689

GnomAD4 genome

AF:

0.712

AC:

108293

AN:

152008

Hom.:

38845

Cov.:

AF XY:

0.714

AC XY:

53091

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.784

Gnomad4 AMR

AF:

0.723

Gnomad4 ASJ

AF:

0.714

Gnomad4 EAS

AF:

0.817

Gnomad4 SAS

AF:

0.735

Gnomad4 FIN

AF:

0.656

Gnomad4 NFE

AF:

0.668

Gnomad4 OTH

AF:

0.701

Alfa

AF:

0.683

Hom.:

74625

Bravo

AF:

0.718

TwinsUK

AF:

0.668

AC:

2476

ALSPAC

AF:

0.659

AC:

2540

ESP6500AA

AF:

0.779

AC:

3432

ESP6500EA

AF:

0.672

AC:

5783

ExAC

AF:

0.716

AC:

86941

Asia WGS

AF:

0.745

AC:

2594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEC23IP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.065

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.12

MetaRNN

Benign

6.5e-7

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

1.4

REVEL

Benign

0.084

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.042

MPC

0.17

ClinPred

0.0065

GERP RS

5.2

Varity_R

0.15

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over