rs74683746

Variant names:

• chr14-39150353-C-G
• rs74683746
• NM_001079537.2:c.474G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-39150353-C-G
• chr14-39150353-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001079537.2(TRAPPC6B):​c.474G>C​(p.Leu158Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,584,124 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (8 hom.)
• Consequence: TRAPPC6B NM_001079537.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.733
• Publications: 1 publications found

Genes affected

TRAPPC6B (HGNC:23066): (trafficking protein particle complex subunit 6B) TRAPPC6B is a component of TRAPP complexes, which are tethering complexes involved in vesicle transport (Kummel et al., 2005 [PubMed 16025134]).[supplied by OMIM, Mar 2008]

TRAPPC6B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics

ENSG00000285830 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-39150353-C-G is Benign according to our data. Variant chr14-39150353-C-G is described in ClinVar as Benign. ClinVar VariationId is 1673738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.733 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00412 (627/152004) while in subpopulation AFR AF = 0.0146 (606/41440). AF 95% confidence interval is 0.0137. There are 6 homozygotes in GnomAd4. There are 281 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079537.2. 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
	TRAPPC6B	NM_001079537.2	MANE Select	c.474G>C	p.Leu158Leu	synonymous	Exon 6 of 6	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.390G>C	p.Leu130Leu	synonymous	Exon 5 of 5	NP_803235.1	Q86SZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC6B	ENST00000330149.10	TSL:1 MANE Select	c.474G>C	p.Leu158Leu	synonymous	Exon 6 of 6	ENSP00000330289.5	Q86SZ2-1
	TRAPPC6B	ENST00000347691.9	TSL:1	c.390G>C	p.Leu130Leu	synonymous	Exon 5 of 5	ENSP00000335171.6	Q86SZ2-2
	TRAPPC6B	ENST00000555269.5	TSL:1	n.*354G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes AF: 0.00412 AC: 626 AN: 151886 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000982 AC: 220 AN: 224036 AF XY: 0.000725

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.000590

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000943

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.000410 AC: 587 AN: 1432120 Hom.: 8 Cov.: 27 AF XY: 0.000383 AC XY: 273 AN XY: 712104

African (AFR) AF: 0.0156 AC: 503 AN: 32222

American (AMR) AF: 0.000668 AC: 27 AN: 40436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25536

East Asian (EAS) AF: 0.00 AC: 0 AN: 39430

South Asian (SAS) AF: 0.0000618 AC: 5 AN: 80886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45088

Middle Eastern (MID) AF: 0.000701 AC: 4 AN: 5708

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1103318

Other (OTH) AF: 0.000723 AC: 43 AN: 59496

GnomAD4 genome AF: 0.00412 AC: 627 AN: 152004 Hom.: 6 Cov.: 32 AF XY: 0.00378 AC XY: 281 AN XY: 74302

African (AFR) AF: 0.0146 AC: 606 AN: 41440

American (AMR) AF: 0.00118 AC: 18 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000294 Hom.: 0

Bravo AF: 0.00495

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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	-0.38
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs74683746; hg19: chr14-39619557;