rs12771873

Variant names:

• chr10-119926047-G-A
• rs12771873
• NM_007190.4:c.2133G>A

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.2133G>A​(p.Ala711Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,609,484 control chromosomes in the GnomAD database, including 6,558 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 (442 hom., cov: 33)
  • Exomes 𝑓: 0.071 (6116 hom.)
• Consequence: SEC23IP NM_007190.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.10
• Publications: 12 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=-0.84).
• BP6: Variant 10-119926047-G-A is Benign according to our data. Variant chr10-119926047-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055417.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 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.2133G>A	p.Ala711Ala	synonymous	Exon 13 of 19	NP_009121.1
	SEC23IP	NM_001411070.1		c.2133G>A	p.Ala711Ala	synonymous	Exon 13 of 19	NP_001397999.1
	SEC23IP	NR_037771.2		n.1653G>A		non_coding_transcript_exon	Exon 12 of 18

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.2133G>A	p.Ala711Ala	synonymous	Exon 13 of 19	ENSP00000358071.3
	SEC23IP	ENST00000705471.1		c.2133G>A	p.Ala711Ala	synonymous	Exon 13 of 19	ENSP00000516127.1

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8391 AN: 152058 Hom.: 442 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.0914

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0440

GnomAD2 exomes AF: 0.0900 AC: 22171 AN: 246450 AF XY: 0.0985

Gnomad AFR exome AF: 0.00942

Gnomad AMR exome AF: 0.0486

Gnomad ASJ exome AF: 0.0449

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.0924

Gnomad NFE exome AF: 0.0554

Gnomad OTH exome AF: 0.0727

GnomAD4 exome AF: 0.0708 AC: 103144 AN: 1457308 Hom.: 6116 Cov.: 31 AF XY: 0.0765 AC XY: 55458 AN XY: 724816

African (AFR) AF: 0.00950 AC: 315 AN: 33142

American (AMR) AF: 0.0455 AC: 1980 AN: 43486

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 1070 AN: 25926

East Asian (EAS) AF: 0.204 AC: 8088 AN: 39622

South Asian (SAS) AF: 0.252 AC: 21590 AN: 85612

European-Finnish (FIN) AF: 0.0887 AC: 4732 AN: 53346

Middle Eastern (MID) AF: 0.0711 AC: 408 AN: 5740

European-Non Finnish (NFE) AF: 0.0544 AC: 60417 AN: 1110284

Other (OTH) AF: 0.0755 AC: 4544 AN: 60150

GnomAD4 genome AF: 0.0552 AC: 8396 AN: 152176 Hom.: 442 Cov.: 33 AF XY: 0.0606 AC XY: 4511 AN XY: 74396

African (AFR) AF: 0.0104 AC: 432 AN: 41530

American (AMR) AF: 0.0370 AC: 565 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1017 AN: 5170

South Asian (SAS) AF: 0.270 AC: 1305 AN: 4826

European-Finnish (FIN) AF: 0.0914 AC: 967 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0557 AC: 3791 AN: 68012

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

Alfa AF: 0.0503 Hom.: 409

Bravo AF: 0.0446

Asia WGS AF: 0.204 AC: 710 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEC23IP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.25
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12771873; hg19: chr10-121685559; COSMIC: COSV64831051; COSMIC: COSV64831051;