rs546233603

Variant names:

• chr7-100155046-C-T
• rs546233603
• NM_018275.5:c.1708G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100155046-C-T
• chr7-100155046-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018275.5(TRAPPC14):​c.1708G>A​(p.Glu570Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: TRAPPC14 NM_018275.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.49
• Publications: 1 publications found

Genes affected

TRAPPC14 (HGNC:25604): (trafficking protein particle complex subunit 14) Enables alpha-tubulin binding activity. Involved in cilium assembly and regulation of cell population proliferation. Located in several cellular components, including microtubule cytoskeleton; midbody; and plasma membrane. Part of TRAPPII protein complex. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

LAMTOR4 (HGNC:33772): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 4) Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cellular response to amino acid stimulus; positive regulation of TOR signaling; and protein localization to lysosome. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4023986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018275.5. 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
	TRAPPC14	NM_018275.5	MANE Select	c.1708G>A	p.Glu570Lys	missense	Exon 11 of 11	NP_060745.3
	TRAPPC14	NM_001303470.2		c.901G>A	p.Glu301Lys	missense	Exon 11 of 11	NP_001290399.1	B3KNS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC14	ENST00000316937.8	TSL:1 MANE Select	c.1708G>A	p.Glu570Lys	missense	Exon 11 of 11	ENSP00000324741.3	Q8WVR3-1
	TRAPPC14	ENST00000394035.6	TSL:1	n.*551G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000377600.3	C9JMZ9
	TRAPPC14	ENST00000394035.6	TSL:1	n.*551G>A		3_prime_UTR	Exon 4 of 4	ENSP00000377600.3	C9JMZ9

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251384 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000527 AC: 77 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.0000660 AC XY: 48 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1111992

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

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

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Pathogenic	0.84
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.5
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Benign	0.032	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.66
MVP		0.66
MPC		0.65
ClinPred		0.46	T
GERP RS		4.5
Varity_R		0.26
gMVP		0.83
Mutation Taster		=73/27	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: rs546233603; hg19: chr7-99752669;