10-119892915-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007190.4(SEC23IP):c.133G>A(p.Ala45Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00178 in 1,613,074 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 26 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 32 hom. )

Consequence

SEC23IP
NM_007190.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032828152).

BP6

Variant 10-119892915-G-A is Benign according to our data. Variant chr10-119892915-G-A is described in ClinVar as [Benign]. Clinvar id is 780914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00974 (1484/152286) while in subpopulation AFR AF= 0.0343 (1424/41550). AF 95% confidence interval is 0.0328. There are 26 homozygotes in gnomad4. There are 705 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 1 of 19	ENST00000369075.8	NP_009121.1	Q9Y6Y8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC23IP	ENST00000369075.8 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 1 of 19	1	NM_007190.4	ENSP00000358071.3	Q9Y6Y8-1
SEC23IP	ENST00000705471.1 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 1 of 19			ENSP00000516127.1	A0A994J542
SEC23IP	ENST00000470478.1 link	n.171G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00974

AC:

1482

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00248

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:

0.0000735

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00253

AC:

633

AN:

249730

Hom.:

AF XY:

0.00187

AC XY:

253

AN XY:

135070

show subpopulations

Gnomad AFR exome

AF:

0.0349

Gnomad AMR exome

AF:

0.00162

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:

0.0000973

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000946

AC:

1382

AN:

1460788

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

595

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.0343

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00197

GnomAD4 genome

AF:

0.00974

AC:

1484

AN:

152286

Hom.:

Cov.:

AF XY:

0.00947

AC XY:

705

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0343

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.000472

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0315

AC:

139

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00309

AC:

375

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SEC23IP-related disorder

Benign:1

Mar 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.080

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.010

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.022

D;.

Sift4G

Benign

0.16

T;T

Polyphen

0.016

B;.

Vest4

0.38

MVP

0.89

MPC

0.14

ClinPred

0.028

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.37

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