Genetic Variant NM_174975.5:c.1180G>C (chr22-30460044-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174975.5(SEC14L3):c.1180G>C(p.Asp394His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SEC14L3
NM_174975.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17451614).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC14L3	NM_174975.5	MANE Select	c.1180G>C	p.Asp394His	missense	Exon 12 of 12	NP_777635.1	Q9UDX4-1
SEC14L3	NM_001257379.2		c.1003G>C	p.Asp335His	missense	Exon 13 of 13	NP_001244308.1	Q9UDX4-2
SEC14L3	NM_001257382.2		c.1003G>C	p.Asp335His	missense	Exon 13 of 13	NP_001244311.1	Q9UDX4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC14L3	ENST00000215812.9	TSL:1 MANE Select	c.1180G>C	p.Asp394His	missense	Exon 12 of 12	ENSP00000215812.5	Q9UDX4-1
SEC14L3	ENST00000401751.5	TSL:1	c.1003G>C	p.Asp335His	missense	Exon 13 of 13	ENSP00000383896.1	Q9UDX4-2
SEC14L3	ENST00000402286.5	TSL:1	c.949G>C	p.Asp317His	missense	Exon 14 of 14	ENSP00000385004.1	Q9UDX4-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251400

AF XY:

0.0000368

show subpopulations

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:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000854

AC:

AN:

1111980

Other (OTH)

AF:

0.0000662

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

Eigen

Benign

0.082

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.79

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.1

PhyloP100

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.79

REVEL

Benign

0.16

Sift

Benign

0.11

Sift4G

Benign

0.10

Polyphen

0.93

Vest4

0.24

MutPred

0.18

Gain of methylation at K395 (P = 0.0578)

MVP

0.83

MPC

0.32

ClinPred

0.095

GERP RS

6.0

Varity_R

0.16

gMVP

0.41

Mutation Taster

=58/42

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over