chr17-77191199-G-A

Variant names:

• chr17-77191199-G-A
• NM_001143998.2:c.232G>A

Variant summary

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

The NM_001143998.2(SEC14L1):​c.232G>A​(p.Val78Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.9e-7 (0 hom.)
• Consequence: SEC14L1 NM_001143998.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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=0.32047796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC14L1	NM_001143998.2	c.232G>A	p.Val78Ile	missense_variant	Exon 5 of 17	ENST00000436233.9	NP_001137470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L1	ENST00000436233.9	c.232G>A	p.Val78Ile	missense_variant	Exon 5 of 17	1	NM_001143998.2	ENSP00000390392.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459668 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726344

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: 9.01e-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

Nov 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232G>A (p.V78I) alteration is located in exon 7 (coding exon 3) of the SEC14L1 gene. This alteration results from a G to A substitution at nucleotide position 232, causing the valine (V) at amino acid position 78 to be replaced by an isoleucine (I). 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	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0087	T;.;T;T;T;.;.;T;.;T
Eigen	Benign	0.048
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;.;.;.;D;D;.;D;D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;L;L;L;L;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.45	.;N;N;.;N;N;.;.;N;.
REVEL	Benign	0.11
Sift	Benign	0.17	.;T;T;.;T;T;.;.;T;.
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T;T;T
Polyphen		0.045, 0.055	.;B;B;B;B;B;.;.;.;.
Vest4		0.32, 0.31, 0.31, 0.32, 0.31, 0.32
MutPred		0.52		Gain of catalytic residue at V78 (P = 0.0135);Gain of catalytic residue at V78 (P = 0.0135);Gain of catalytic residue at V78 (P = 0.0135);Gain of catalytic residue at V78 (P = 0.0135);Gain of catalytic residue at V78 (P = 0.0135);Gain of catalytic residue at V78 (P = 0.0135);.;.;.;.;
MVP		0.17
MPC		0.44
ClinPred		0.82	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.30

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: chr17-75187281;