10-119909144-T-G

Variant names:

• chr10-119909144-T-G
• rs3740570
• NM_007190.4:c.1191+14T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007190.4(SEC23IP):​c.1191+14T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 1,553,532 control chromosomes in the GnomAD database, including 5,982 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 0.054 (421 hom., cov: 32)
  • Exomes 𝑓: 0.069 (5561 hom.)
• Consequence: SEC23IP NM_007190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.1191+14T>G		intron_variant	Intron 5 of 18	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.1191+14T>G		intron_variant	Intron 5 of 18	1	NM_007190.4	ENSP00000358071.3
SEC23IP	ENST00000705471.1	c.1191+14T>G		intron_variant	Intron 5 of 18			ENSP00000516127.1
SEC23IP	ENST00000446561.1	c.304-2900T>G		intron_variant	Intron 2 of 4	3		ENSP00000396906.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8286 AN: 152188 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0430

GnomAD2 exomes AF: 0.0863 AC: 19374 AN: 224624 AF XY: 0.0935

Gnomad AFR exome AF: 0.00950

Gnomad AMR exome AF: 0.0479

Gnomad ASJ exome AF: 0.0446

Gnomad EAS exome AF: 0.188

Gnomad FIN exome AF: 0.0919

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0715

GnomAD4 exome AF: 0.0693 AC: 97107 AN: 1401224 Hom.: 5561 Cov.: 23 AF XY: 0.0746 AC XY: 52185 AN XY: 699092

African (AFR) AF: 0.00919 AC: 288 AN: 31344

American (AMR) AF: 0.0421 AC: 1565 AN: 37206

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 995 AN: 24770

East Asian (EAS) AF: 0.194 AC: 7622 AN: 39234

South Asian (SAS) AF: 0.243 AC: 19423 AN: 80018

European-Finnish (FIN) AF: 0.0883 AC: 4685 AN: 53082

Middle Eastern (MID) AF: 0.0699 AC: 390 AN: 5580

European-Non Finnish (NFE) AF: 0.0540 AC: 57878 AN: 1071952

Other (OTH) AF: 0.0734 AC: 4261 AN: 58038

GnomAD4 genome AF: 0.0544 AC: 8290 AN: 152308 Hom.: 421 Cov.: 32 AF XY: 0.0597 AC XY: 4446 AN XY: 74476

African (AFR) AF: 0.0103 AC: 430 AN: 41574

American (AMR) AF: 0.0369 AC: 565 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3468

East Asian (EAS) AF: 0.185 AC: 958 AN: 5184

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4826

European-Finnish (FIN) AF: 0.0917 AC: 974 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0557 AC: 3788 AN: 68016

Other (OTH) AF: 0.0444 AC: 94 AN: 2116

Alfa AF: 0.0376 Hom.: 56

Bravo AF: 0.0440

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.34
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs3740570; hg19: chr10-121668656; COSMIC: COSV64831045; COSMIC: COSV64831045;