17-77194848-G-T

Variant names:

• chr17-77194848-G-T
• NM_001143998.2:c.646G>T

Variant summary

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

The NM_001143998.2(SEC14L1):​c.646G>T​(p.Gly216Trp) variant causes a missense change. 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: 33)
• Consequence: SEC14L1 NM_001143998.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28

Genes affected

SEC14L1 (HGNC:10698): (SEC14 like lipid binding 1) The protein encoded by this gene belongs to the SEC14 cytosolic factor family. It has similarity to yeast SEC14 and to Japanese flying squid RALBP which suggests a possible role of the gene product in an intracellular transport system. Multiple alternatively spliced transcript variants have been found for this gene; some variants represent read-through transcripts that include exons from the upstream gene C17orf86. [provided by RefSeq, Feb 2011]

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=0.38289073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC14L1	NM_001143998.2	c.646G>T	p.Gly216Trp	missense_variant	Exon 7 of 17	ENST00000436233.9	NP_001137470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L1	ENST00000436233.9	c.646G>T	p.Gly216Trp	missense_variant	Exon 7 of 17	1	NM_001143998.2	ENSP00000390392.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.646G>T (p.G216W) alteration is located in exon 9 (coding exon 5) of the SEC14L1 gene. This alteration results from a G to T substitution at nucleotide position 646, causing the glycine (G) at amino acid position 216 to be replaced by a tryptophan (W). 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	0.23
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T;.;T;T;T;.;.;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;.;.;.;T;T;.;T;T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.0052	T
MutationAssessor	Uncertain	2.8	.;M;M;M;M;M;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	.;N;N;.;N;N;.;N;.
REVEL	Benign	0.25
Sift	Uncertain	0.011	.;D;D;.;D;D;.;D;.
Sift4G	Uncertain	0.017	D;D;D;D;D;D;D;D;D
Polyphen		0.99, 0.99	.;D;D;D;D;D;.;.;.
Vest4		0.56, 0.56, 0.56, 0.56, 0.56, 0.56, 0.55
MutPred		0.27		Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);.;.;.;
MVP		0.80
MPC		1.4
ClinPred		0.85	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.091
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr17-75190930;