22-30462181-C-T

Position:

• chr22-30462181-C-T

Variant summary

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

The NM_174975.5(SEC14L3):​c.676G>A​(p.Glu226Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC14L3 NM_174975.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L3	NM_174975.5	c.676G>A	p.Glu226Lys	missense_variant	9/12	ENST00000215812.9	NP_777635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L3	ENST00000215812.9	c.676G>A	p.Glu226Lys	missense_variant	9/12	1	NM_174975.5	ENSP00000215812.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

The c.676G>A (p.E226K) alteration is located in exon 9 (coding exon 9) of the SEC14L3 gene. This alteration results from a G to A substitution at nucleotide position 676, causing the glutamic acid (E) at amino acid position 226 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	Benign	0.21
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.;.;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T;.;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	.;L;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.091
Sift	Benign	0.054	T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.15	.;B;.;.;.
Vest4		0.53
MutPred		0.56		.;Gain of MoRF binding (P = 0.0044);.;.;.;
MVP		0.52
MPC		0.14
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.76
gMVP		0.69

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: chr22-30858168; COSMIC: COSV53181144;