10-119914716-AT-ATT

Variant names:

• chr10-119914716-A-AT
• rs34824340
• NM_007190.4:c.1313-6dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_007190.4(SEC23IP):​c.1313-6dupT variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 3 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: Benign. The variant received -8 ACMG points.

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

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.1313-6dupT		splice_region intron	N/A	NP_009121.1
	SEC23IP	NM_001411070.1		c.1313-6dupT		splice_region intron	N/A	NP_001397999.1
	SEC23IP	NR_037771.2		n.833-6dupT		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.1313-6dupT		splice_region intron	N/A	ENSP00000358071.3
	SEC23IP	ENST00000462222.1	TSL:3	n.225dupT		non_coding_transcript_exon	Exon 1 of 3
	SEC23IP	ENST00000705471.1		c.1313-6dupT		splice_region intron	N/A	ENSP00000516127.1

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

GnomAD2 exomes AF: 0.106 AC: 26295 AN: 248734 AF XY: 0.112

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 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

African (AFR) AF: 0.116 AC: 3853 AN: 33320

American (AMR) AF: 0.0737 AC: 3280 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3852 AN: 26010

East Asian (EAS) AF: 0.00151 AC: 60 AN: 39638

South Asian (SAS) AF: 0.176 AC: 15123 AN: 85912

European-Finnish (FIN) AF: 0.0621 AC: 3314 AN: 53338

Middle Eastern (MID) AF: 0.136 AC: 784 AN: 5746

European-Non Finnish (NFE) AF: 0.117 AC: 129497 AN: 1107440

Other (OTH) AF: 0.118 AC: 7118 AN: 60182

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

African (AFR) AF: 0.120 AC: 4980 AN: 41450

American (AMR) AF: 0.0949 AC: 1449 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3464

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.166 AC: 799 AN: 4818

European-Finnish (FIN) AF: 0.0581 AC: 614 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7737 AN: 67972

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0628 Hom.: 89

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs34824340; hg19: chr10-121674228;