chr10-119919501-A-C

Variant names:

• chr10-119919501-A-C
• rs2475298
• NM_007190.4:c.1930A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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 Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 45 publications found

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

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=0.08865866).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	NM_007190.4	MANE Select	c.1930A>C	p.Lys644Gln	missense	Exon 11 of 19	NP_009121.1
	SEC23IP	NM_001411070.1		c.1930A>C	p.Lys644Gln	missense	Exon 11 of 19	NP_001397999.1
	SEC23IP	NR_037771.2		n.1450A>C		non_coding_transcript_exon	Exon 10 of 18

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.1930A>C	p.Lys644Gln	missense	Exon 11 of 19	ENSP00000358071.3
	SEC23IP	ENST00000705471.1		c.1930A>C	p.Lys644Gln	missense	Exon 11 of 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 v4.9

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
PhyloP100		4.0
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2475298; hg19: chr10-121679013;