rs10131298

Variant names:

• chr14-103102277-T-A
• rs10131298
• NM_001077594.2:c.554T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-103102277-T-A
• chr14-103102277-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077594.2(EXOC3L4):​c.554T>A​(p.Leu185His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,580,606 control chromosomes in the GnomAD database, including 47,530 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4639 hom., cov: 34)
  • Exomes 𝑓: 0.24 (42891 hom.)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024491847).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L4	NM_001077594.2	MANE Select	c.554T>A	p.Leu185His	missense	Exon 3 of 12	NP_001071062.1
	EXOC3L4	NM_001394941.1		c.554T>A	p.Leu185His	missense	Exon 4 of 13	NP_001381870.1
	EXOC3L4	NM_001394942.1		c.554T>A	p.Leu185His	missense	Exon 4 of 13	NP_001381871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L4	ENST00000688303.1	MANE Select	c.554T>A	p.Leu185His	missense	Exon 3 of 12	ENSP00000509130.1
	EXOC3L4	ENST00000380069.7	TSL:1	c.554T>A	p.Leu185His	missense	Exon 2 of 11	ENSP00000369409.3
	EXOC3L4	ENST00000687959.1		c.554T>A	p.Leu185His	missense	Exon 4 of 13	ENSP00000508483.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36928 AN: 152066 Hom.: 4628 Cov.: 34

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.240 AC: 47122 AN: 196358 AF XY: 0.244

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.257

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.244 AC: 348539 AN: 1428422 Hom.: 42891 Cov.: 36 AF XY: 0.245 AC XY: 173603 AN XY: 708518

African (AFR) AF: 0.261 AC: 8580 AN: 32832

American (AMR) AF: 0.177 AC: 7360 AN: 41510

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6457 AN: 25694

East Asian (EAS) AF: 0.243 AC: 9240 AN: 38018

South Asian (SAS) AF: 0.264 AC: 21884 AN: 83044

European-Finnish (FIN) AF: 0.226 AC: 9826 AN: 43572

Middle Eastern (MID) AF: 0.215 AC: 1228 AN: 5722

European-Non Finnish (NFE) AF: 0.245 AC: 269194 AN: 1098786

Other (OTH) AF: 0.249 AC: 14770 AN: 59244

GnomAD4 genome AF: 0.243 AC: 36975 AN: 152184 Hom.: 4639 Cov.: 34 AF XY: 0.240 AC XY: 17886 AN XY: 74414

African (AFR) AF: 0.257 AC: 10681 AN: 41548

American (AMR) AF: 0.202 AC: 3089 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1298 AN: 5160

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4822

European-Finnish (FIN) AF: 0.221 AC: 2339 AN: 10602

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16447 AN: 67966

Other (OTH) AF: 0.264 AC: 559 AN: 2116

Alfa AF: 0.240 Hom.: 1349

Bravo AF: 0.244

TwinsUK AF: 0.249 AC: 922

ALSPAC AF: 0.246 AC: 949

ESP6500AA AF: 0.264 AC: 1155

ESP6500EA AF: 0.242 AC: 2075

ExAC AF: 0.219 AC: 26025

Asia WGS AF: 0.276 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.023
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.046
Sift	Benign	0.053	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.14
MPC		0.041
ClinPred		0.0077	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.74
Mutation Taster		=95/5	polymorphism (auto)

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: rs10131298; hg19: chr14-103568614; COSMIC: COSV66295382; COSMIC: COSV66295382;