16-4988197-T-A

Position:

• chr16-4988197-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014692.2(SEC14L5):​c.262T>A​(p.Trp88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SEC14L5 NM_014692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67

Genes affected

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

ACMG classification

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=0.119047016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L5	NM_014692.2	c.262T>A	p.Trp88Arg	missense_variant	4/16	ENST00000251170.12	NP_055507.1
SEC14L5	XM_024450497.2	c.262T>A	p.Trp88Arg	missense_variant	4/16		XP_024306265.1
SEC14L5	XM_024450498.2	c.262T>A	p.Trp88Arg	missense_variant	4/16		XP_024306266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L5	ENST00000251170.12	c.262T>A	p.Trp88Arg	missense_variant	4/16	1	NM_014692.2	ENSP00000251170	P1
SEC14L5	ENST00000587469.1	c.262T>A	p.Trp88Arg	missense_variant	3/5	4		ENSP00000468423

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446468 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 719466

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: 9.08e-7

Gnomad4 OTH exome AF: 0.00

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

Jan 29, 2024

The c.262T>A (p.W88R) alteration is located in exon 4 (coding exon 3) of the SEC14L5 gene. This alteration results from a T to A substitution at nucleotide position 262, causing the tryptophan (W) at amino acid position 88 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	0.26
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.026	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.84	N;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	2.3	N;.
REVEL	Benign	0.068
Sift	Benign	0.74	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.24
MutPred		0.63		Loss of catalytic residue at L86 (P = 0.0058);Loss of catalytic residue at L86 (P = 0.0058);
MVP		0.13
MPC		0.097
ClinPred		0.59	D
GERP RS		3.2
Varity_R		0.13
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-5038198;