NM_001077594.2:c.478G>C

Variant names:

• chr14-103102201-G-C
• rs1318284277
• NM_001077594.2:c.478G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077594.2(EXOC3L4):​c.478G>C​(p.Val160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

EXOC3L4 (HGNC:20120): (exocyst complex component 3 like 4) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization and exocytosis. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084181756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077594.2. 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
	EXOC3L4	NM_001077594.2	MANE Select	c.478G>C	p.Val160Leu	missense	Exon 3 of 12	NP_001071062.1	Q17RC7
	EXOC3L4	NM_001394941.1		c.478G>C	p.Val160Leu	missense	Exon 4 of 13	NP_001381870.1	Q17RC7
	EXOC3L4	NM_001394942.1		c.478G>C	p.Val160Leu	missense	Exon 4 of 13	NP_001381871.1	Q17RC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L4	ENST00000688303.1	MANE Select	c.478G>C	p.Val160Leu	missense	Exon 3 of 12	ENSP00000509130.1	Q17RC7
	EXOC3L4	ENST00000380069.7	TSL:1	c.478G>C	p.Val160Leu	missense	Exon 2 of 11	ENSP00000369409.3	Q17RC7
	EXOC3L4	ENST00000687959.1		c.478G>C	p.Val160Leu	missense	Exon 4 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.042
Sift	Benign	0.32	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.068	B
Vest4		0.094
MutPred		0.57		Loss of helix (P = 0.079)
MVP		0.040
MPC		0.036
ClinPred		0.071	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.22
Mutation Taster		=92/8	polymorphism

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: rs1318284277; hg19: chr14-103568538;