10-119892930-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_007190.4(SEC23IP):c.148C>T(p.Leu50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,612,998 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (4 hom.)
• Consequence: SEC23IP NM_007190.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.853

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-119892930-C-T is Benign according to our data. Variant chr10-119892930-C-T is described in ClinVar as [Benign]. Clinvar id is 719744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.853 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23IP	NM_007190.4	c.148C>T	p.Leu50=	synonymous_variant	1/19	ENST00000369075.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23IP	ENST00000369075.8	c.148C>T	p.Leu50=	synonymous_variant	1/19	1	NM_007190.4	P4
SEC23IP	ENST00000705471.1	c.148C>T	p.Leu50=	synonymous_variant	1/19			A1
SEC23IP	ENST00000470478.1	n.186C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 209 AN: 152254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00124 AC: 308 AN: 248916 Hom.: 1 AF XY: 0.00120 AC XY: 162 AN XY: 134690

Gnomad AFR exome AF: 0.000373

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00218 AC: 3182 AN: 1460626 Hom.: 4 Cov.: 31 AF XY: 0.00212 AC XY: 1541 AN XY: 726616

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00261

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152372 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74520

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00223

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00152 Hom.: 0

Bravo AF: 0.00162

EpiCase AF: 0.00235

EpiControl AF: 0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	8.1
Dann	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs141132251; hg19: chr10-121652442;