14-103102410-C-G

Variant names:

• chr14-103102410-C-G
• rs10142287
• NM_001077594.2:c.687C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001077594.2(EXOC3L4):​c.687C>G​(p.Pro229Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,532,906 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (188 hom., cov: 34)
  • Exomes 𝑓: 0.0031 (165 hom.)
• Consequence: EXOC3L4 NM_001077594.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.91
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-103102410-C-G is Benign according to our data. Variant chr14-103102410-C-G is described in ClinVar as Benign. ClinVar VariationId is 1279821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L4	NM_001077594.2	MANE Select	c.687C>G	p.Pro229Pro	synonymous	Exon 3 of 12	NP_001071062.1	Q17RC7
	EXOC3L4	NM_001394941.1		c.687C>G	p.Pro229Pro	synonymous	Exon 4 of 13	NP_001381870.1	Q17RC7
	EXOC3L4	NM_001394942.1		c.687C>G	p.Pro229Pro	synonymous	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.687C>G	p.Pro229Pro	synonymous	Exon 3 of 12	ENSP00000509130.1	Q17RC7
	EXOC3L4	ENST00000380069.7	TSL:1	c.687C>G	p.Pro229Pro	synonymous	Exon 2 of 11	ENSP00000369409.3	Q17RC7
	EXOC3L4	ENST00000687959.1		c.687C>G	p.Pro229Pro	synonymous	Exon 4 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4166 AN: 152172 Hom.: 187 Cov.: 34

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.00435 AC: 551 AN: 126658 AF XY: 0.00392

Gnomad AFR exome AF: 0.0980

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00451

GnomAD4 exome AF: 0.00311 AC: 4300 AN: 1380620 Hom.: 165 Cov.: 36 AF XY: 0.00273 AC XY: 1864 AN XY: 682934

African (AFR) AF: 0.103 AC: 3012 AN: 29106

American (AMR) AF: 0.00526 AC: 187 AN: 35552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24614

East Asian (EAS) AF: 0.0000586 AC: 2 AN: 34156

South Asian (SAS) AF: 0.00156 AC: 123 AN: 78924

European-Finnish (FIN) AF: 0.000775 AC: 27 AN: 34834

Middle Eastern (MID) AF: 0.00166 AC: 9 AN: 5412

European-Non Finnish (NFE) AF: 0.000506 AC: 547 AN: 1080402

Other (OTH) AF: 0.00682 AC: 393 AN: 57620

GnomAD4 genome AF: 0.0274 AC: 4168 AN: 152286 Hom.: 188 Cov.: 34 AF XY: 0.0263 AC XY: 1958 AN XY: 74466

African (AFR) AF: 0.0951 AC: 3950 AN: 41554

American (AMR) AF: 0.00771 AC: 118 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68004

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.00165 Hom.: 1

Bravo AF: 0.0312

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.087
DANN	Benign	0.58
PhyloP100		-4.9
Mutation Taster		=100/0	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: rs10142287; hg19: chr14-103568747;