22-30461449-GAT-TAC

Variant names:

• chr22-30461449-GAT-TAC
• NM_174975.5:c.940_942delATCinsGTA
• SEC14L3 p.Ile314Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_174975.5(SEC14L3):​c.940_942delATCinsGTA​(p.Ile314Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC14L3 NM_174975.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.70
• Publications: 0 publications found

Genes affected

SEC14L3 (HGNC:18655): (SEC14 like lipid binding 3) The protein encoded by this gene is highly similar to the protein encoded by the Saccharomyces cerevisiae SEC14 gene. The SEC14 protein is a phophatidylinositol transfer protein that is essential for biogenesis of Golgi-derived transport vesicles, and thus is required for the export of yeast secretory proteins from the Golgi complex. The specific function of this protein has not yet been determined. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174975.5. 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
	SEC14L3	NM_174975.5	MANE Select	c.940_942delATCinsGTA	p.Ile314Val	missense	N/A	NP_777635.1	Q9UDX4-1
	SEC14L3	NM_001376914.1		c.763_765delATCinsGTA	p.Ile255Val	missense	N/A	NP_001363843.1	B5MC44
	SEC14L3	NM_001257379.2		c.763_765delATCinsGTA	p.Ile255Val	missense	N/A	NP_001244308.1	Q9UDX4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L3	ENST00000215812.9	TSL:1 MANE Select	c.940_942delATCinsGTA	p.Ile314Val	missense	N/A	ENSP00000215812.5	Q9UDX4-1
	SEC14L3	ENST00000401751.5	TSL:1	c.763_765delATCinsGTA	p.Ile255Val	missense	N/A	ENSP00000383896.1	Q9UDX4-2
	SEC14L3	ENST00000402286.5	TSL:1	c.709_711delATCinsGTA	p.Ile237Val	missense	N/A	ENSP00000385004.1	Q9UDX4-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-30857436;