NM_001143998.2:c.100C>G

Variant names:

• chr17-77190839-C-G
• rs776854628
• NM_001143998.2:c.100C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001143998.2(SEC14L1):​c.100C>G​(p.Pro34Ala) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC14L1 NM_001143998.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.85
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L1	NM_001143998.2	MANE Select	c.100C>G	p.Pro34Ala	missense	Exon 4 of 17	NP_001137470.2	Q92503-1
	SEC14L1	NM_001144001.2		c.-3C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	NP_001137473.2	Q92503-3
	SEC14L1	NM_001039573.3		c.100C>G	p.Pro34Ala	missense	Exon 4 of 18	NP_001034662.3	Q92503-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L1	ENST00000436233.9	TSL:1 MANE Select	c.100C>G	p.Pro34Ala	missense	Exon 4 of 17	ENSP00000390392.3	Q92503-1
	SEC14L1	ENST00000443798.8	TSL:1	c.100C>G	p.Pro34Ala	missense	Exon 4 of 18	ENSP00000406030.3	Q92503-2
	SEC14L1	ENST00000585618.5	TSL:1	c.100C>G	p.Pro34Ala	missense	Exon 4 of 17	ENSP00000466581.1	Q92503-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Monoclonal B-Cell Lymphocytosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.63		Gain of sheet (P = 0.0827)
MVP		0.85
MPC		1.5
ClinPred		1.0	D
GERP RS		5.1
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.54

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

Other links and lift over

dbSNP: rs776854628; hg19: chr17-75186921;