NM_007190.4:c.32G>A

Variant names:

• chr10-119892814-G-A
• NM_007190.4:c.32G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007190.4(SEC23IP):​c.32G>A​(p.Gly11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.32G>A	p.Gly11Asp	missense	Exon 1 of 19	NP_009121.1	Q9Y6Y8-1
	SEC23IP	NM_001411070.1		c.32G>A	p.Gly11Asp	missense	Exon 1 of 19	NP_001397999.1	A0A994J542
	SEC23IP	NR_037771.2		n.85G>A		non_coding_transcript_exon	Exon 1 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.32G>A	p.Gly11Asp	missense	Exon 1 of 19	ENSP00000358071.3	Q9Y6Y8-1
	SEC23IP	ENST00000875162.1		c.32G>A	p.Gly11Asp	missense	Exon 1 of 20	ENSP00000545221.1
	SEC23IP	ENST00000970232.1		c.32G>A	p.Gly11Asp	missense	Exon 1 of 19	ENSP00000640291.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460358 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726406

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111538

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.073
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	1.6	L
PhyloP100		2.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.13	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.016	D
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.51
MutPred		0.12		Loss of glycosylation at S10 (P = 0.032)
MVP		0.92
MPC		0.43
ClinPred		0.94	D
GERP RS		4.1
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.13
gMVP		0.28
Mutation Taster		=89/11	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

hg19: chr10-121652326;