Variant 17-77200671-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.1007A>G(p.Lys336Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEC14L1
NM_001143998.2 missense, splice_region

Scores

Splicing: ADA: 0.02490

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

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:

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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=0.25697827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L1	NM_001143998.2 linkuse as main transcript	c.1007A>G	p.Lys336Arg	missense_variant, splice_region_variant	9/17	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.1007A>G	p.Lys336Arg	missense_variant, splice_region_variant	9/17	1	NM_001143998.2	ENSP00000390392		Q92503-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

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

Nov 16, 2021

The c.1007A>G (p.K336R) alteration is located in exon 11 (coding exon 7) of the SEC14L1 gene. This alteration results from a A to G substitution at nucleotide position 1007, causing the lysine (K) at amino acid position 336 to be replaced by an arginine (R). 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

0.064

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

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

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.010

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.021

MetaRNN

Benign

0.26

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

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.52

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.21

Sift

Benign

0.33

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

Sift4G

Benign

0.37

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

Polyphen

0.041, 0.051

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

Vest4

0.22, 0.21, 0.21, 0.22, 0.20, 0.20

MutPred

0.47

Loss of ubiquitination at K336 (P = 0.0116);Loss of ubiquitination at K336 (P = 0.0116);Loss of ubiquitination at K336 (P = 0.0116);Loss of ubiquitination at K336 (P = 0.0116);Loss of ubiquitination at K336 (P = 0.0116);Loss of ubiquitination at K336 (P = 0.0116);.;.;

MVP

0.75

MPC

0.45

ClinPred

0.59

GERP RS

5.1

Varity_R

0.11

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.025

dbscSNV1_RF

Benign

0.15

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.28

Position offset: 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