Genetic Variant SEC23IP:p.Pro231Leu (chr10-119898955-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007190.4(SEC23IP):c.692C>T(p.Pro231Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,427,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P231R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SEC23IP
NM_007190.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.99

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18727091).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC23IP	NM_007190.4	MANE Select	c.692C>T	p.Pro231Leu	missense	Exon 2 of 19	NP_009121.1	Q9Y6Y8-1
SEC23IP	NM_001411070.1		c.692C>T	p.Pro231Leu	missense	Exon 2 of 19	NP_001397999.1	A0A994J542
SEC23IP	NR_037771.2		n.217-3844C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.692C>T	p.Pro231Leu	missense	Exon 2 of 19	ENSP00000358071.3	Q9Y6Y8-1
SEC23IP	ENST00000875162.1		c.692C>T	p.Pro231Leu	missense	Exon 2 of 20	ENSP00000545221.1
SEC23IP	ENST00000970232.1		c.692C>T	p.Pro231Leu	missense	Exon 2 of 19	ENSP00000640291.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1427680

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33070

American (AMR)

AF:

0.00

AC:

AN:

42642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24414

East Asian (EAS)

AF:

0.00

AC:

AN:

39486

South Asian (SAS)

AF:

0.00

AC:

AN:

82890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101054

Other (OTH)

AF:

0.0000168

AC:

AN:

59422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.73

M_CAP

Benign

0.012

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

4.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

REVEL

Benign

0.095

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Polyphen

0.67

Vest4

0.21

MutPred

0.26

Loss of glycosylation at P231 (P = 0.0432)

MVP

0.36

MPC

0.13

ClinPred

0.94

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.21

Mutation Taster

=63/37

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over