10-119912139-T-C

Variant names:

• chr10-119912139-T-C
• rs17099368
• NM_007190.4:c.1287T>C

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.1287T>C​(p.Asp429Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 1,613,904 control chromosomes in the GnomAD database, including 6,496 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 (431 hom., cov: 32)
  • Exomes 𝑓: 0.071 (6065 hom.)
• Consequence: SEC23IP NM_007190.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0180
• Publications: 13 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=-0.64).
• BP6: Variant 10-119912139-T-C is Benign according to our data. Variant chr10-119912139-T-C is described in ClinVar as [Benign]. Clinvar id is 3055672.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.018 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.1287T>C	p.Asp429Asp	synonymous_variant	Exon 6 of 19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.1287T>C	p.Asp429Asp	synonymous_variant	Exon 6 of 19	1	NM_007190.4	ENSP00000358071.3
SEC23IP	ENST00000705471.1	c.1287T>C	p.Asp429Asp	synonymous_variant	Exon 6 of 19			ENSP00000516127.1
SEC23IP	ENST00000446561.1	c.399T>C	p.Asp133Asp	synonymous_variant	Exon 3 of 5	3		ENSP00000396906.1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8317 AN: 152128 Hom.: 431 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: 0.269

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0889 AC: 22358 AN: 251358 AF XY: 0.0977

Gnomad AFR exome AF: 0.00947

Gnomad AMR exome AF: 0.0490

Gnomad ASJ exome AF: 0.0445

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.0925

Gnomad NFE exome AF: 0.0555

Gnomad OTH exome AF: 0.0721

GnomAD4 exome AF: 0.0705 AC: 103073 AN: 1461658 Hom.: 6065 Cov.: 31 AF XY: 0.0763 AC XY: 55508 AN XY: 727126

African (AFR) AF: 0.00956 AC: 320 AN: 33474

American (AMR) AF: 0.0461 AC: 2062 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 1067 AN: 26136

East Asian (EAS) AF: 0.195 AC: 7732 AN: 39690

South Asian (SAS) AF: 0.252 AC: 21714 AN: 86220

European-Finnish (FIN) AF: 0.0886 AC: 4734 AN: 53410

Middle Eastern (MID) AF: 0.0706 AC: 407 AN: 5764

European-Non Finnish (NFE) AF: 0.0544 AC: 60517 AN: 1111860

Other (OTH) AF: 0.0749 AC: 4520 AN: 60382

GnomAD4 genome AF: 0.0547 AC: 8323 AN: 152246 Hom.: 431 Cov.: 32 AF XY: 0.0600 AC XY: 4467 AN XY: 74436

African (AFR) AF: 0.0103 AC: 429 AN: 41560

American (AMR) AF: 0.0369 AC: 565 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3470

East Asian (EAS) AF: 0.185 AC: 958 AN: 5182

South Asian (SAS) AF: 0.270 AC: 1298 AN: 4814

European-Finnish (FIN) AF: 0.0916 AC: 971 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0557 AC: 3788 AN: 68010

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

Alfa AF: 0.0507 Hom.: 216

Bravo AF: 0.0441

Asia WGS AF: 0.202 AC: 701 AN: 3478

EpiCase AF: 0.0565

EpiControl AF: 0.0555

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	-0.64
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		0.018
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs17099368; hg19: chr10-121671651; COSMIC: COSV64831026; COSMIC: COSV64831026;