10-119914716-AT-ATT

Position:

• chr10-119914716-AT-ATT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_007190.4(SEC23IP):​c.1313-6dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,608,142 control chromosomes in the GnomAD database, including 11,058 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (943 hom., cov: 30)
  • Exomes 𝑓: 0.11 (10115 hom.)
• Consequence: SEC23IP NM_007190.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23IP	NM_007190.4	c.1313-6dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000369075.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23IP	ENST00000369075.8	c.1313-6dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_007190.4	P4
SEC23IP	ENST00000446561.1	c.425-6dup		splice_polypyrimidine_tract_variant, intron_variant		3
SEC23IP	ENST00000705471.1	c.1313-6dup		splice_polypyrimidine_tract_variant, intron_variant				A1
SEC23IP	ENST00000462222.1	n.225dup		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16420 AN: 151932 Hom.: 940 Cov.: 30

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.106 AC: 26295 AN: 248734 Hom.: 1640 AF XY: 0.112 AC XY: 15049 AN XY: 134386

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.00148

Gnomad SAS exome AF: 0.177

Gnomad FIN exome AF: 0.0603

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.115 AC: 166881 AN: 1456094 Hom.: 10115 Cov.: 30 AF XY: 0.117 AC XY: 84986 AN XY: 724702

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0737

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.00151

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0621

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.108 AC: 16425 AN: 152048 Hom.: 943 Cov.: 30 AF XY: 0.106 AC XY: 7886 AN XY: 74318

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0949

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0581

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs34824340; hg19: chr10-121674228;