7-100155800-GC-TG

Variant names:

• chr7-100155800-GC-TG
• NM_018275.5:c.1265_1266delGCinsCA
• TRAPPC14 p.Arg422Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018275.5(TRAPPC14):​c.1265_1266delGCinsCA​(p.Arg422Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R422H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC14 NM_018275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1265_1266delGCinsCA	p.Arg422Pro	missense	N/A	NP_060745.3
	TRAPPC14	NM_001303470.2		c.458_459delGCinsCA	p.Arg153Pro	missense	N/A	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.1265_1266delGCinsCA	p.Arg422Pro	missense	N/A	ENSP00000324741.3	Q8WVR3-1
	TRAPPC14	ENST00000394035.6	TSL:1	n.*108_*109delGCinsCA		non_coding_transcript_exon	Exon 2 of 4	ENSP00000377600.3	C9JMZ9
	TRAPPC14	ENST00000394035.6	TSL:1	n.*108_*109delGCinsCA		3_prime_UTR	Exon 2 of 4	ENSP00000377600.3	C9JMZ9

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-99753423;