7-100157720-C-T

Variant names:

• chr7-100157720-C-T
• rs117793118
• NM_018275.5:c.550G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018275.5(TRAPPC14):​c.550G>A​(p.Val184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,614,222 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (31 hom.)
• Consequence: TRAPPC14 NM_018275.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.17
• Publications: 7 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00498724).
• BP6: Variant 7-100157720-C-T is Benign according to our data. Variant chr7-100157720-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 31 AR gene

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.550G>A	p.Val184Ile	missense	Exon 3 of 11	NP_060745.3
	TRAPPC14	NM_001303470.2		c.-258G>A		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.550G>A	p.Val184Ile	missense	Exon 3 of 11	ENSP00000324741.3	Q8WVR3-1
	TRAPPC14	ENST00000950372.1		c.550G>A	p.Val184Ile	missense	Exon 3 of 11	ENSP00000620431.1
	TRAPPC14	ENST00000950373.1		c.550G>A	p.Val184Ile	missense	Exon 3 of 11	ENSP00000620432.1

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 473 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00359 AC: 903 AN: 251452 AF XY: 0.00396

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.0105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00408

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00488 AC: 7137 AN: 1461882 Hom.: 31 Cov.: 32 AF XY: 0.00508 AC XY: 3694 AN XY: 727240

African (AFR) AF: 0.00102 AC: 34 AN: 33480

American (AMR) AF: 0.00201 AC: 90 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00945 AC: 247 AN: 26136

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

South Asian (SAS) AF: 0.00729 AC: 629 AN: 86258

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53412

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.00519 AC: 5769 AN: 1112008

Other (OTH) AF: 0.00556 AC: 336 AN: 60396

GnomAD4 genome AF: 0.00310 AC: 473 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.00289 AC XY: 215 AN XY: 74502

African (AFR) AF: 0.00115 AC: 48 AN: 41582

American (AMR) AF: 0.00268 AC: 41 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00472 AC: 321 AN: 68034

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00445 Hom.: 3

Bravo AF: 0.00322

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00570 AC: 49

ExAC AF: 0.00358 AC: 435

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00628

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	TRAPPC14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.2
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.13
Sift	Benign	0.73	T
Sift4G	Benign	0.42	T
Polyphen		0.15	B
Vest4		0.20
MVP		0.28
MPC		1.0
ClinPred		0.015	T
GERP RS		5.9
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.25
Mutation Taster		=260/40	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: rs117793118; hg19: chr7-99755343; COSMIC: COSV100385722; COSMIC: COSV100385722;