16-4996363-C-G

Position:

• chr16-4996363-C-G

Variant summary

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

The ENST00000251170.12(SEC14L5):​c.683C>G​(p.Ala228Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000712 in 1,405,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A228V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SEC14L5 ENST00000251170.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

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=0.16872561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L5	NM_014692.2	c.683C>G	p.Ala228Gly	missense_variant	7/16	ENST00000251170.12	NP_055507.1
SEC14L5	XM_024450497.2	c.683C>G	p.Ala228Gly	missense_variant	7/16		XP_024306265.1
SEC14L5	XM_024450498.2	c.683C>G	p.Ala228Gly	missense_variant	7/16		XP_024306266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L5	ENST00000251170.12	c.683C>G	p.Ala228Gly	missense_variant	7/16	1	NM_014692.2	ENSP00000251170	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1405214 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 694184

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: 9.24e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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 06, 2021

The c.683C>G (p.A228G) alteration is located in exon 7 (coding exon 6) of the SEC14L5 gene. This alteration results from a C to G substitution at nucleotide position 683, causing the alanine (A) at amino acid position 228 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.85	D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.17	T
Sift4G	Benign	0.12	T
Polyphen		0.075	B
Vest4		0.24
MutPred		0.34		Gain of disorder (P = 0.0939);
MVP		0.39
MPC		0.059
ClinPred		0.82	D
GERP RS		4.3
Varity_R		0.087
gMVP		0.36

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: chr16-5046364;