Variant 16-4990771-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014692.2(SEC14L5):c.350A>G(p.His117Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SEC14L5
NM_014692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.85

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L5	NM_014692.2 linkuse as main transcript	c.350A>G	p.His117Arg	missense_variant	5/16	ENST00000251170.12	NP_055507.1	O43304
SEC14L5	XM_024450497.2 linkuse as main transcript	c.350A>G	p.His117Arg	missense_variant	5/16		XP_024306265.1
SEC14L5	XM_024450498.2 linkuse as main transcript	c.350A>G	p.His117Arg	missense_variant	5/16		XP_024306266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L5	ENST00000251170.12 linkuse as main transcript	c.350A>G	p.His117Arg	missense_variant	5/16	1	NM_014692.2	ENSP00000251170.6		O43304
SEC14L5	ENST00000587469.1 linkuse as main transcript	c.350A>G	p.His117Arg	missense_variant	4/5	4		ENSP00000468423.1		K7ERV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000826

AC:

AN:

242106

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131556

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723888

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000827

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

Aug 27, 2024

The c.350A>G (p.H117R) alteration is located in exon 5 (coding exon 4) of the SEC14L5 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the histidine (H) at amino acid position 117 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

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.9

M;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-7.1

D;.

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.80

Loss of glycosylation at T115 (P = 0.1067);Loss of glycosylation at T115 (P = 0.1067);

MVP

0.48

MPC

0.24

ClinPred

0.99

GERP RS

4.4

Varity_R

0.85

gMVP

0.80

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