Variant chr22-30461346-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_174975.5(SEC14L3):c.1045G>A(p.Glu349Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,458,246 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

SEC14L3
NM_174975.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Variant links:

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]

SEC14L3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L3	NM_174975.5 link	c.1045G>A	p.Glu349Lys	missense_variant	11/12	ENST00000215812.9	NP_777635.1	Q9UDX4-1Q6XCI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L3	ENST00000215812.9 link	c.1045G>A	p.Glu349Lys	missense_variant	11/12	1	NM_174975.5	ENSP00000215812.5		Q9UDX4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000525

AC:

AN:

247574

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

133632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000447

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1458246

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

725168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000203

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:

0.0000495

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000942

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.1045G>A (p.E349K) alteration is located in exon 11 (coding exon 11) of the SEC14L3 gene. This alteration results from a G to A substitution at nucleotide position 1045, causing the glutamic acid (E) at amino acid position 349 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.099

.;T;.;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D;.;D

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.80

D;D;D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.3

.;M;.;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.6

D;D;D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.016

D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

0.98

.;D;.;.;.

Vest4

0.86

MVP

0.64

MPC

0.55

ClinPred

0.77

GERP RS

5.7

Varity_R

0.64

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over