rs34826964

Variant names:

• chr10-119933734-A-G
• rs34826964
• NM_007190.4:c.2970A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_007190.4(SEC23IP):​c.2970A>G​(p.Thr990Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,594,410 control chromosomes in the GnomAD database, including 6,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.055 (432 hom., cov: 33)
  • Exomes 𝑓: 0.069 (5857 hom.)
• Consequence: SEC23IP NM_007190.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.549
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-119933734-A-G is Benign according to our data. Variant chr10-119933734-A-G is described in ClinVar as [Benign]. Clinvar id is 3056457.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.549 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.2970A>G	p.Thr990Thr	synonymous_variant	Exon 18 of 19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.2970A>G	p.Thr990Thr	synonymous_variant	Exon 18 of 19	1	NM_007190.4	ENSP00000358071.3
SEC23IP	ENST00000705471.1	c.2967A>G	p.Thr989Thr	synonymous_variant	Exon 18 of 19			ENSP00000516127.1
SEC23IP	ENST00000475542.1	n.516A>G		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8330 AN: 152168 Hom.: 432 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0885 AC: 22192 AN: 250620 AF XY: 0.0973

Gnomad AFR exome AF: 0.00949

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.0443

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.0922

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0711

GnomAD4 exome AF: 0.0688 AC: 99230 AN: 1442124 Hom.: 5857 Cov.: 27 AF XY: 0.0748 AC XY: 53775 AN XY: 718684

African (AFR) AF: 0.00950 AC: 315 AN: 33156

American (AMR) AF: 0.0457 AC: 2039 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 1045 AN: 25990

East Asian (EAS) AF: 0.194 AC: 7648 AN: 39458

South Asian (SAS) AF: 0.250 AC: 21312 AN: 85330

European-Finnish (FIN) AF: 0.0885 AC: 4719 AN: 53328

Middle Eastern (MID) AF: 0.0701 AC: 401 AN: 5722

European-Non Finnish (NFE) AF: 0.0524 AC: 57419 AN: 1094788

Other (OTH) AF: 0.0726 AC: 4332 AN: 59690

GnomAD4 genome AF: 0.0547 AC: 8335 AN: 152286 Hom.: 432 Cov.: 33 AF XY: 0.0601 AC XY: 4473 AN XY: 74448

African (AFR) AF: 0.0104 AC: 431 AN: 41570

American (AMR) AF: 0.0369 AC: 565 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 131 AN: 3472

East Asian (EAS) AF: 0.185 AC: 958 AN: 5166

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4822

European-Finnish (FIN) AF: 0.0917 AC: 973 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0557 AC: 3791 AN: 68026

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0512 Hom.: 143

Bravo AF: 0.0441

Asia WGS AF: 0.201 AC: 700 AN: 3474

EpiCase AF: 0.0563

EpiControl AF: 0.0553

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SEC23IP-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.2
DANN	Benign	0.74
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs34826964; hg19: chr10-121693246; COSMIC: COSV64831058;