chr10-119898487-C-G

Variant names:

• chr10-119898487-C-G
• rs750824114
• NM_007190.4:c.224C>G

Variant summary

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

The NM_007190.4(SEC23IP):​c.224C>G​(p.Ser75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921

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=0.32346603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.224C>G	p.Ser75Cys	missense_variant	Exon 2 of 19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.224C>G	p.Ser75Cys	missense_variant	Exon 2 of 19	1	NM_007190.4	ENSP00000358071.3
SEC23IP	ENST00000705471.1	c.224C>G	p.Ser75Cys	missense_variant	Exon 2 of 19			ENSP00000516127.1
SEC23IP	ENST00000470478.1	n.*160C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251414 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135878

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.033	D;D
Polyphen		0.99	D;.
Vest4		0.30
MutPred		0.40		Loss of glycosylation at S75 (P = 0.021);Loss of glycosylation at S75 (P = 0.021);
MVP		0.94
MPC		0.39
ClinPred		0.77	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs750824114; hg19: chr10-121657999;