NM_001143998.2:c.520G>C

Variant names:

• chr17-77194722-G-C
• NM_001143998.2:c.520G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001143998.2(SEC14L1):​c.520G>C​(p.Gly174Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC14L1 NM_001143998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.41

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC14L1	NM_001143998.2	c.520G>C	p.Gly174Arg	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.520G>C	p.Gly174Arg	missense_variant	Exon 7 of 17	1	NM_001143998.2	ENSP00000390392.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.029	T;.;T;T;T;.;.;T;.;T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D;.;.;.;D;D;.;D;D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.0	.;M;M;M;M;M;.;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.9	.;D;D;.;D;D;.;.;D;.
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	.;D;D;.;D;D;.;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;D;D;D;.;.;.;.
Vest4		0.85, 0.83, 0.83, 0.83, 0.85, 0.81, 0.80
MutPred		0.71		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);.;.;.;.;
MVP		0.91
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.81

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: chr17-75190804;