Variant 16-4991979-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014692.2(SEC14L5):c.616C>G(p.His206Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,587,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SEC14L5
NM_014692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.72

Variant links:

Genes affected

SEC14L5 (HGNC:29032): (SEC14 like lipid binding 5)

SEC14L5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009636462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SEC14L5	NM_014692.2 linkuse as main transcript	c.616C>G	p.His206Asp	missense_variant	6/16	ENST00000251170.12	NP_055507.1
SEC14L5	XM_024450497.2 linkuse as main transcript	c.616C>G	p.His206Asp	missense_variant	6/16		XP_024306265.1
SEC14L5	XM_024450498.2 linkuse as main transcript	c.616C>G	p.His206Asp	missense_variant	6/16		XP_024306266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L5	ENST00000251170.12 linkuse as main transcript	c.616C>G	p.His206Asp	missense_variant	6/16	1	NM_014692.2	ENSP00000251170	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000155

AC:

AN:

207098

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

113124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000189

GnomAD4 exome

AF:

0.0000251

AC:

AN:

1435780

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

713002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000807

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000141

AC:

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

May 13, 2024

The c.616C>G (p.H206D) alteration is located in exon 6 (coding exon 5) of the SEC14L5 gene. This alteration results from a C to G substitution at nucleotide position 616, causing the histidine (H) at amino acid position 206 to be replaced by an aspartic acid (D). 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

0.056

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.029

DANN

Benign

0.46

DEOGEN2

Benign

0.019

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.15

M_CAP

Benign

0.022

MetaRNN

Benign

0.0096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.64

REVEL

Benign

0.033

Sift

Benign

0.63

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.13

MutPred

0.20

Gain of phosphorylation at T211 (P = 0.1628);

MVP

0.067

MPC

0.035

ClinPred

0.026

GERP RS

-4.1

Varity_R

0.032

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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