10-119892805-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007190.4(SEC23IP):c.23G>C(p.Gly8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,459,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28574067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23IP	NM_007190.4	c.23G>C	p.Gly8Ala	missense_variant	1/19	ENST00000369075.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23IP	ENST00000369075.8	c.23G>C	p.Gly8Ala	missense_variant	1/19	1	NM_007190.4	P4
SEC23IP	ENST00000705471.1	c.23G>C	p.Gly8Ala	missense_variant	1/19			A1
SEC23IP	ENST00000470478.1	n.61G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245666 Hom.: 0 AF XY: 0.00000750 AC XY: 1 AN XY: 133260

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1459826 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.23G>C (p.G8A) alteration is located in exon 1 (coding exon 1) of the SEC23IP gene. This alteration results from a G to C substitution at nucleotide position 23, causing the glycine (G) at amino acid position 8 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	0.060
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.79	T;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.45	N;.
REVEL	Uncertain	0.43
Sift	Benign	0.057	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.58	P;.
Vest4		0.33
MutPred		0.19		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.91
MPC		0.60
ClinPred		0.63	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.059
gMVP		0.13

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: rs1466750858; hg19: chr10-121652317;