10-119898686-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007190.4(SEC23IP):c.423A>T(p.Gln141His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.55

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053676665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23IP	NM_007190.4	c.423A>T	p.Gln141His	missense_variant	2/19	ENST00000369075.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23IP	ENST00000369075.8	c.423A>T	p.Gln141His	missense_variant	2/19	1	NM_007190.4	P4
SEC23IP	ENST00000705471.1	c.423A>T	p.Gln141His	missense_variant	2/19			A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jan 04, 2022

The c.423A>T (p.Q141H) alteration is located in exon 2 (coding exon 2) of the SEC23IP gene. This alteration results from a A to T substitution at nucleotide position 423, causing the glutamine (Q) at amino acid position 141 to be replaced by a histidine (H). 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	0.096
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	0.26
Dann	Benign	0.62
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.054	T;T
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.73	N;.
REVEL	Benign	0.19
Sift	Benign	0.56	T;.
Sift4G	Benign	0.32	T;T
Polyphen		0.0010	B;.
Vest4		0.15
MutPred		0.12		Gain of glycosylation at P142 (P = 0.1702);Gain of glycosylation at P142 (P = 0.1702);
MVP		0.63
MPC		0.12
ClinPred		0.034	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-121658198;