16-4990890-A-G

Position:

• chr16-4990890-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014692.2(SEC14L5):​c.469A>G​(p.Lys157Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC14L5 NM_014692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L5	NM_014692.2	c.469A>G	p.Lys157Glu	missense_variant	5/16	ENST00000251170.12	NP_055507.1
SEC14L5	XM_024450497.2	c.469A>G	p.Lys157Glu	missense_variant	5/16		XP_024306265.1
SEC14L5	XM_024450498.2	c.469A>G	p.Lys157Glu	missense_variant	5/16		XP_024306266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L5	ENST00000251170.12	c.469A>G	p.Lys157Glu	missense_variant	5/16	1	NM_014692.2	ENSP00000251170	P1
SEC14L5	ENST00000587469.1	c.469A>G	p.Lys157Glu	missense_variant	4/5	4		ENSP00000468423

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.469A>G (p.K157E) 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 469, causing the lysine (K) at amino acid position 157 to be replaced by a glutamic acid (E). 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	0.19
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.18
Sift	Benign	0.23	T;.
Sift4G	Benign	0.53	T;T
Polyphen		0.065	B;.
Vest4		0.63
MutPred		0.48		Loss of MoRF binding (P = 0.0071);Loss of MoRF binding (P = 0.0071);
MVP		0.26
MPC		0.10
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.32
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-5040891;