chr7-100157657-C-G

Variant names:

• chr7-100157657-C-G
• rs149225624
• NM_018275.5:c.613G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018275.5(TRAPPC14):​c.613G>C​(p.Glu205Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRAPPC14 NM_018275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22
• 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]

TRAPPC14 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21879447).

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.613G>C	p.Glu205Gln	missense	Exon 3 of 11	NP_060745.3
	TRAPPC14	NM_001303470.2		c.-195G>C		5_prime_UTR	Exon 3 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.613G>C	p.Glu205Gln	missense	Exon 3 of 11	ENSP00000324741.3	Q8WVR3-1
	TRAPPC14	ENST00000950372.1		c.613G>C	p.Glu205Gln	missense	Exon 3 of 11	ENSP00000620431.1
	TRAPPC14	ENST00000950373.1		c.613G>C	p.Glu205Gln	missense	Exon 3 of 11	ENSP00000620432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.15
Sift	Benign	0.19	T
Sift4G	Uncertain	0.045	D
Polyphen		0.97	D
Vest4		0.17
MutPred		0.19		Gain of MoRF binding (P = 0.0569)
MVP		0.33
MPC		1.4
ClinPred		0.82	D
GERP RS		5.9
PromoterAI		-0.030	Neutral
Varity_R		0.15
gMVP		0.28
Mutation Taster		=282/18	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: rs149225624; hg19: chr7-99755280;