NM_174975.5:c.907C>T

Variant names:

• chr22-30461559-G-A
• rs752174541
• NM_174975.5:c.907C>T

Variant summary

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

The NM_174975.5(SEC14L3):​c.907C>T​(p.Leu303Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000019 (0 hom.)
• Consequence: SEC14L3 NM_174975.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.42
• Publications: 1 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: MetaRNN computational evidence supports a deleterious effect, 0.747

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.907C>T	p.Leu303Phe	missense	Exon 10 of 12	NP_777635.1	Q9UDX4-1
	SEC14L3	NM_001376914.1		c.730C>T	p.Leu244Phe	missense	Exon 11 of 13	NP_001363843.1	B5MC44
	SEC14L3	NM_001257379.2		c.730C>T	p.Leu244Phe	missense	Exon 11 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.907C>T	p.Leu303Phe	missense	Exon 10 of 12	ENSP00000215812.5	Q9UDX4-1
	SEC14L3	ENST00000401751.5	TSL:1	c.730C>T	p.Leu244Phe	missense	Exon 11 of 13	ENSP00000383896.1	Q9UDX4-2
	SEC14L3	ENST00000402286.5	TSL:1	c.676C>T	p.Leu226Phe	missense	Exon 12 of 14	ENSP00000385004.1	Q9UDX4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251214 AF XY: 0.0000589

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461890 Hom.: 0 Cov.: 35 AF XY: 0.0000303 AC XY: 22 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		9.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.54
Sift	Benign	0.076	T
Sift4G	Benign	0.065	T
Polyphen		0.86	P
Vest4		0.88
MutPred		0.53		Loss of catalytic residue at L303 (P = 0.2918)
MVP		0.48
MPC		0.59
ClinPred		0.80	D
GERP RS		5.9
Varity_R		0.75
gMVP		0.61
Mutation Taster		=21/79	disease causing

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

Other links and lift over

dbSNP: rs752174541; hg19: chr22-30857546;