NM_174975.5:c.935C>A

Variant names:

• chr22-30461456-G-T
• rs144684185
• NM_174975.5:c.935C>A

Variant summary

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

The NM_174975.5(SEC14L3):​c.935C>A​(p.Ala312Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A312V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SEC14L3 NM_174975.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 4 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 2 ACMG points.

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

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.935C>A	p.Ala312Glu	missense	Exon 11 of 12	NP_777635.1	Q9UDX4-1
	SEC14L3	NM_001376914.1		c.758C>A	p.Ala253Glu	missense	Exon 12 of 13	NP_001363843.1	B5MC44
	SEC14L3	NM_001257379.2		c.758C>A	p.Ala253Glu	missense	Exon 12 of 13	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.935C>A	p.Ala312Glu	missense	Exon 11 of 12	ENSP00000215812.5	Q9UDX4-1
	SEC14L3	ENST00000401751.5	TSL:1	c.758C>A	p.Ala253Glu	missense	Exon 12 of 13	ENSP00000383896.1	Q9UDX4-2
	SEC14L3	ENST00000402286.5	TSL:1	c.704C>A	p.Ala235Glu	missense	Exon 13 of 14	ENSP00000385004.1	Q9UDX4-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250542 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461460 Hom.: 0 Cov.: 63 AF XY: 0.0000206 AC XY: 15 AN XY: 726988

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111754

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.6
DANN	Benign	0.83
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.94
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.067
Sift	Benign	0.080	T
Sift4G	Benign	0.13	T
Polyphen		0.010	B
Vest4		0.32
MutPred		0.57		Gain of disorder (P = 0.0593)
MVP		0.23
MPC		0.15
ClinPred		0.11	T
GERP RS		-2.5
Varity_R		0.31
gMVP		0.51
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs144684185; hg19: chr22-30857443;