22-30461313-C-T

Variant names:

• chr22-30461313-C-T
• rs201231956
• NM_174975.5:c.1078G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_174975.5(SEC14L3):​c.1078G>A​(p.Val360Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,585,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: SEC14L3 NM_174975.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.741
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07095757).

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.1078G>A	p.Val360Ile	missense	Exon 11 of 12	NP_777635.1	Q9UDX4-1
	SEC14L3	NM_001376914.1		c.901G>A	p.Val301Ile	missense	Exon 12 of 13	NP_001363843.1	B5MC44
	SEC14L3	NM_001257379.2		c.901G>A	p.Val301Ile	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.1078G>A	p.Val360Ile	missense	Exon 11 of 12	ENSP00000215812.5	Q9UDX4-1
	SEC14L3	ENST00000401751.5	TSL:1	c.901G>A	p.Val301Ile	missense	Exon 12 of 13	ENSP00000383896.1	Q9UDX4-2
	SEC14L3	ENST00000402286.5	TSL:1	c.847G>A	p.Val283Ile	missense	Exon 13 of 14	ENSP00000385004.1	Q9UDX4-3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 23 AN: 227348 AF XY: 0.000115

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: 0.000184

Gnomad OTH exome AF: 0.000183

GnomAD4 exome AF: 0.000113 AC: 162 AN: 1432968 Hom.: 0 Cov.: 30 AF XY: 0.000118 AC XY: 84 AN XY: 709998

African (AFR) AF: 0.000122 AC: 4 AN: 32710

American (AMR) AF: 0.00 AC: 0 AN: 41238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24004

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39470

South Asian (SAS) AF: 0.000124 AC: 10 AN: 80832

European-Finnish (FIN) AF: 0.0000383 AC: 2 AN: 52274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.000122 AC: 134 AN: 1097734

Other (OTH) AF: 0.000186 AC: 11 AN: 59116

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000955 Hom.: 0

Bravo AF: 0.0000680

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000157 AC: 19

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	Benign	0.065
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.7
DANN	Benign	0.70
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.93	L
PhyloP100		0.74
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.048
Sift	Benign	0.41	T
Sift4G	Benign	0.27	T
Polyphen		0.0050	B
Vest4		0.15
MVP		0.10
MPC		0.41
ClinPred		0.045	T
GERP RS		4.6
Varity_R		0.062
gMVP		0.19
Mutation Taster		=78/22	polymorphism

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: rs201231956; hg19: chr22-30857300; COSMIC: COSV99307072; COSMIC: COSV99307072;