14-103102429-C-G

Variant names:

• chr14-103102429-C-G
• rs762358612
• NM_001077594.2:c.706C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077594.2(EXOC3L4):​c.706C>G​(p.Arg236Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R236C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0411748).

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.706C>G	p.Arg236Gly	missense	Exon 3 of 12	NP_001071062.1	Q17RC7
	EXOC3L4	NM_001394941.1		c.706C>G	p.Arg236Gly	missense	Exon 4 of 13	NP_001381870.1	Q17RC7
	EXOC3L4	NM_001394942.1		c.706C>G	p.Arg236Gly	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.706C>G	p.Arg236Gly	missense	Exon 3 of 12	ENSP00000509130.1	Q17RC7
	EXOC3L4	ENST00000380069.7	TSL:1	c.706C>G	p.Arg236Gly	missense	Exon 2 of 11	ENSP00000369409.3	Q17RC7
	EXOC3L4	ENST00000687959.1		c.706C>G	p.Arg236Gly	missense	Exon 4 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364644 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 673906

African (AFR) AF: 0.00 AC: 0 AN: 28160

American (AMR) AF: 0.00 AC: 0 AN: 33222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23978

East Asian (EAS) AF: 0.00 AC: 0 AN: 33134

South Asian (SAS) AF: 0.00 AC: 0 AN: 76706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5186

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1073118

Other (OTH) AF: 0.00 AC: 0 AN: 56942

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.78
DEOGEN2	Benign	0.00011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.48
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.039
Sift	Benign	0.94	T
Sift4G	Benign	0.15	T
Polyphen		0.053	B
Vest4		0.067
MutPred		0.60		Loss of solvent accessibility (P = 0.0299)
MVP		0.014
MPC		1.2
ClinPred		0.031	T
GERP RS		-1.9
Varity_R		0.055
gMVP		0.34
Mutation Taster		=88/12	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: rs762358612; hg19: chr14-103568766;