NM_007190.4:c.625C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007190.4(SEC23IP):​c.625C>G​(p.Pro209Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SEC23IP NM_007190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09532654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4	c.625C>G	p.Pro209Ala	missense_variant	Exon 2 of 19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8	c.625C>G	p.Pro209Ala	missense_variant	Exon 2 of 19	1	NM_007190.4	ENSP00000358071.3
SEC23IP	ENST00000705471.1	c.625C>G	p.Pro209Ala	missense_variant	Exon 2 of 19			ENSP00000516127.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454138 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	9.7
DANN	Benign	0.39
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.095	T;T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.22
Sift	Benign	0.60	T;.
Sift4G	Benign	0.33	T;D
Polyphen		0.0010	B;.
Vest4		0.24
MutPred		0.21		Loss of glycosylation at P209 (P = 0.0074);Loss of glycosylation at P209 (P = 0.0074);
MVP		0.87
MPC		0.12
ClinPred		0.068	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-121658400;