NM_007190.4:c.625C>T

Variant names:

• chr10-119898888-C-T
• rs148955366
• NM_007190.4:c.625C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_007190.4(SEC23IP):​c.625C>T​(p.Pro209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,606,386 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (75 hom.)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.33
• Publications: 5 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028744638).
• BP6: Variant 10-119898888-C-T is Benign according to our data. Variant chr10-119898888-C-T is described in ClinVar as Benign. ClinVar VariationId is 771886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	NM_007190.4	MANE Select	c.625C>T	p.Pro209Ser	missense	Exon 2 of 19	NP_009121.1	Q9Y6Y8-1
	SEC23IP	NM_001411070.1		c.625C>T	p.Pro209Ser	missense	Exon 2 of 19	NP_001397999.1	A0A994J542
	SEC23IP	NR_037771.2		n.217-3911C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.625C>T	p.Pro209Ser	missense	Exon 2 of 19	ENSP00000358071.3	Q9Y6Y8-1
	SEC23IP	ENST00000875162.1		c.625C>T	p.Pro209Ser	missense	Exon 2 of 20	ENSP00000545221.1
	SEC23IP	ENST00000970232.1		c.625C>T	p.Pro209Ser	missense	Exon 2 of 19	ENSP00000640291.1

Frequencies

GnomAD3 genomes AF: 0.00841 AC: 1280 AN: 152138 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00616

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00974

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00895 AC: 2197 AN: 245384 AF XY: 0.00905

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0359

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.00809 AC: 11771 AN: 1454130 Hom.: 75 Cov.: 32 AF XY: 0.00803 AC XY: 5811 AN XY: 723690

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.00432 AC: 193 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 340 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00373 AC: 322 AN: 86226

European-Finnish (FIN) AF: 0.0348 AC: 1596 AN: 45898

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5768

European-Non Finnish (NFE) AF: 0.00787 AC: 8748 AN: 1111898

Other (OTH) AF: 0.00844 AC: 509 AN: 60342

GnomAD4 genome AF: 0.00841 AC: 1280 AN: 152256 Hom.: 7 Cov.: 32 AF XY: 0.00912 AC XY: 679 AN XY: 74430

African (AFR) AF: 0.00130 AC: 54 AN: 41552

American (AMR) AF: 0.00615 AC: 94 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.0366 AC: 388 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00975 AC: 663 AN: 68032

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00802 Hom.: 8

Bravo AF: 0.00545

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00802 AC: 69

ExAC AF: 0.00901 AC: 1094

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.00954

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SEC23IP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0029	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	0.34	N
PhyloP100		2.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.22
Sift	Benign	0.50	T
Sift4G	Benign	0.29	T
Polyphen		0.025	B
Vest4		0.20
MVP		0.87
MPC		0.13
ClinPred		0.011	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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: rs148955366; hg19: chr10-121658400; COSMIC: COSV100957182; COSMIC: COSV100957182;