10-119919501-A-C

Position:

• chr10-119919501-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007190.4(SEC23IP):​c.1930A>C​(p.Lys644Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. K644E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08865866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.1930A>C	p.Lys644Gln	missense_variant	11/19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.1930A>C	p.Lys644Gln	missense_variant	11/19	1	NM_007190.4	ENSP00000358071.3
SEC23IP	ENST00000705471.1	c.1930A>C	p.Lys644Gln	missense_variant	11/19			ENSP00000516127.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.080
Sift	Benign	0.16	T
Sift4G	Benign	0.56	T
Polyphen		0.019	B
Vest4		0.060
MutPred		0.32		Loss of ubiquitination at K644 (P = 0.0098);
MVP		0.19
MPC		0.15
ClinPred		0.43	T
GERP RS		5.2
Varity_R		0.13
gMVP		0.20

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: rs2475298; hg19: chr10-121679013;