Variant 17-77191278-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143998.2(SEC14L1):c.311A>G(p.Asn104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SEC14L1
NM_001143998.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

SEC14L1 (HGNC:10698): (SEC14 like lipid binding 1) The protein encoded by this gene belongs to the SEC14 cytosolic factor family. It has similarity to yeast SEC14 and to Japanese flying squid RALBP which suggests a possible role of the gene product in an intracellular transport system. Multiple alternatively spliced transcript variants have been found for this gene; some variants represent read-through transcripts that include exons from the upstream gene C17orf86. [provided by RefSeq, Feb 2011]

SEC14L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11836153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L1	NM_001143998.2 linkuse as main transcript	c.311A>G	p.Asn104Ser	missense_variant	5/17	ENST00000436233.9	NP_001137470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L1	ENST00000436233.9 linkuse as main transcript	c.311A>G	p.Asn104Ser	missense_variant	5/17	1	NM_001143998.2	ENSP00000390392		Q92503-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251480

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.311A>G (p.N104S) alteration is located in exon 7 (coding exon 3) of the SEC14L1 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the asparagine (N) at amino acid position 104 to be replaced by a serine (S). 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

0.043

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.44

DEOGEN2

Benign

0.0040

T;.;T;T;T;.;.;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

D;.;.;.;D;D;.;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.075

.;N;N;N;N;N;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

0.64

.;N;N;.;N;N;.;.;N

REVEL

Benign

0.13

Sift

Benign

1.0

.;T;T;.;T;T;.;.;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T

Polyphen

0.0050, 0.0040

.;B;B;B;B;B;.;.;.

Vest4

0.17, 0.16, 0.16, 0.14, 0.16

MutPred

0.42

Loss of catalytic residue at N104 (P = 0.0108);Loss of catalytic residue at N104 (P = 0.0108);Loss of catalytic residue at N104 (P = 0.0108);Loss of catalytic residue at N104 (P = 0.0108);Loss of catalytic residue at N104 (P = 0.0108);Loss of catalytic residue at N104 (P = 0.0108);.;.;.;

MVP

0.42

MPC

0.43

ClinPred

0.10

GERP RS

5.0

Varity_R

0.089

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over