16-4987647-G-A

Position:

• chr16-4987647-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014692.2(SEC14L5):​c.154G>A​(p.Val52Met) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEC14L5 NM_014692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.238

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27626938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L5	NM_014692.2	c.154G>A	p.Val52Met	missense_variant	3/16	ENST00000251170.12	NP_055507.1
SEC14L5	XM_024450497.2	c.154G>A	p.Val52Met	missense_variant	3/16		XP_024306265.1
SEC14L5	XM_024450498.2	c.154G>A	p.Val52Met	missense_variant	3/16		XP_024306266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L5	ENST00000251170.12	c.154G>A	p.Val52Met	missense_variant	3/16	1	NM_014692.2	ENSP00000251170	P1
SEC14L5	ENST00000587469.1	c.154G>A	p.Val52Met	missense_variant	2/5	4		ENSP00000468423

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400840 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 691998

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 11, 2023

The c.154G>A (p.V52M) alteration is located in exon 3 (coding exon 2) of the SEC14L5 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the valine (V) at amino acid position 52 to be replaced by a methionine (M). 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	0.093
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T;.
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.29
Sift	Benign	0.058	T;.
Sift4G	Uncertain	0.060	T;T
Polyphen		0.75	P;.
Vest4		0.29
MutPred		0.75		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.41
MPC		0.16
ClinPred		0.44	T
GERP RS		2.5
Varity_R		0.048
gMVP		0.31

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

Other links and lift over

dbSNP: rs1377086706; hg19: chr16-5037648;