NM_001077594.2:c.262C>T

Variant names:

• chr14-103100481-C-T
• rs373963350
• NM_001077594.2:c.262C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001077594.2(EXOC3L4):​c.262C>T​(p.Arg88Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.202
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11754009).

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.262C>T	p.Arg88Trp	missense	Exon 2 of 12	NP_001071062.1	Q17RC7
	EXOC3L4	NM_001394941.1		c.262C>T	p.Arg88Trp	missense	Exon 3 of 13	NP_001381870.1	Q17RC7
	EXOC3L4	NM_001394942.1		c.262C>T	p.Arg88Trp	missense	Exon 3 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.262C>T	p.Arg88Trp	missense	Exon 2 of 12	ENSP00000509130.1	Q17RC7
	EXOC3L4	ENST00000380069.7	TSL:1	c.262C>T	p.Arg88Trp	missense	Exon 1 of 11	ENSP00000369409.3	Q17RC7
	EXOC3L4	ENST00000687959.1		c.262C>T	p.Arg88Trp	missense	Exon 3 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes AF: 0.0000525 AC: 8 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000482 AC: 12 AN: 249210 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000979

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461012 Hom.: 0 Cov.: 34 AF XY: 0.0000482 AC XY: 35 AN XY: 726808

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111904

Other (OTH) AF: 0.000116 AC: 7 AN: 60382

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74390

African (AFR) AF: 0.0000724 AC: 3 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.20
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.27
MVP		0.28
MPC		0.044
ClinPred		0.38	T
GERP RS		-0.15
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.36
Mutation Taster		=100/0	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: rs373963350; hg19: chr14-103566818;