rs1052289

Positions:

• chr10-119940743-C-T

Variant summary

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

The NM_007190.4(SEC23IP):​c.*178C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,704 control chromosomes in the GnomAD database, including 22,638 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 0.54 (22637 hom., cov: 30)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SEC23IP NM_007190.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.*178C>T		3_prime_UTR_variant	19/19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.*178C>T		3_prime_UTR_variant	19/19	1	NM_007190.4	ENSP00000358071	P4
SEC23IP	ENST00000705471.1	c.*178C>T		3_prime_UTR_variant	19/19			ENSP00000516127	A1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82096 AN: 151584 Hom.: 22615 Cov.: 30

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.542 AC: 82161 AN: 151698 Hom.: 22637 Cov.: 30 AF XY: 0.540 AC XY: 40039 AN XY: 74098

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.552

Alfa AF: 0.504 Hom.: 31738

Bravo AF: 0.556

Asia WGS AF: 0.469 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.69

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: rs1052289; hg19: chr10-121700255;