rs3740569

Positions:

• chr10-119908989-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007190.4(SEC23IP):​c.1102-52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,195,348 control chromosomes in the GnomAD database, including 5,351 homozygotes. 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: 𝑓 0.055 (431 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4920 hom.)
• Consequence: SEC23IP NM_007190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.1102-52C>A		intron_variant		ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.1102-52C>A		intron_variant		1	NM_007190.4	ENSP00000358071	P4
SEC23IP	ENST00000446561.1	c.304-3055C>A		intron_variant		3		ENSP00000396906
SEC23IP	ENST00000705471.1	c.1102-52C>A		intron_variant				ENSP00000516127	A1

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8390 AN: 152044 Hom.: 431 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0441

GnomAD4 exome AF: 0.0749 AC: 78089 AN: 1043184 Hom.: 4920 Cov.: 13 AF XY: 0.0812 AC XY: 43530 AN XY: 536236

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0445

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.0881

Gnomad4 NFE exome AF: 0.0554

Gnomad4 OTH exome AF: 0.0745

GnomAD4 genome AF: 0.0552 AC: 8396 AN: 152164 Hom.: 431 Cov.: 32 AF XY: 0.0606 AC XY: 4504 AN XY: 74368

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.0557

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0547 Hom.: 48

Bravo AF: 0.0445

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.55

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: rs3740569; hg19: chr10-121668501; COSMIC: COSV64831727; COSMIC: COSV64831727;