Variant 10-119898888-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007190.4(SEC23IP):c.625C>T(p.Pro209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,606,386 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 75 hom. )

Consequence

SEC23IP
NM_007190.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028744638).

BP6

Variant 10-119898888-C-T is Benign according to our data. Variant chr10-119898888-C-T is described in ClinVar as [Benign]. Clinvar id is 771886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23IP	NM_007190.4 linkuse as main transcript	c.625C>T	p.Pro209Ser	missense_variant	2/19	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.625C>T	p.Pro209Ser	missense_variant	2/19	1	NM_007190.4	ENSP00000358071.3		Q9Y6Y8-1
SEC23IP	ENST00000705471.1 linkuse as main transcript	c.625C>T	p.Pro209Ser	missense_variant	2/19			ENSP00000516127.1		A0A994J542

Frequencies

GnomAD3 genomes

AF:

0.00841

AC:

1280

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0366

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00974

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00895

AC:

2197

AN:

245384

Hom.:

AF XY:

0.00905

AC XY:

1204

AN XY:

133098

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00443

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00370

Gnomad FIN exome

AF:

0.0359

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.00809

AC:

11771

AN:

1454130

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

5811

AN XY:

723690

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00373

Gnomad4 FIN exome

AF:

0.0348

Gnomad4 NFE exome

AF:

0.00787

Gnomad4 OTH exome

AF:

0.00844

GnomAD4 genome

AF:

0.00841

AC:

1280

AN:

152256

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

679

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.0366

Gnomad4 NFE

AF:

0.00975

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00841

Hom.:

Bravo

AF:

0.00545

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00901

AC:

1094

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.00954

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SEC23IP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 04, 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

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.69

N;.

REVEL

Benign

0.22

Sift

Benign

0.50

T;.

Sift4G

Benign

0.29

T;D

Polyphen

0.025

B;.

Vest4

0.20

MVP

0.87

MPC

0.13

ClinPred

0.011

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.15

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