7-100156720-C-T

Variant names:

• chr7-100156720-C-T
• rs143162409
• NM_018275.5:c.994-4G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_018275.5(TRAPPC14):​c.994-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,608,836 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: TRAPPC14 NM_018275.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004517
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.16

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]

MIR4658 (HGNC:41673): (microRNA 4658) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-100156720-C-T is Benign according to our data. Variant chr7-100156720-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044098.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC14	NM_018275.5	c.994-4G>A		splice_region_variant, intron_variant	Intron 6 of 10	ENST00000316937.8	NP_060745.3
TRAPPC14	NM_001303470.2	c.187-4G>A		splice_region_variant, intron_variant	Intron 6 of 10		NP_001290399.1
MIR4658	NR_039802.1	n.-51G>A		upstream_gene_variant
MIR4658	unassigned_transcript_1285	n.-87G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC14	ENST00000316937.8	c.994-4G>A		splice_region_variant, intron_variant	Intron 6 of 10	1	NM_018275.5	ENSP00000324741.3

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 182 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00132 AC: 325 AN: 245348 Hom.: 0 AF XY: 0.00133 AC XY: 176 AN XY: 132496

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00160

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000373

Gnomad FIN exome AF: 0.0000945

Gnomad NFE exome AF: 0.00141

Gnomad OTH exome AF: 0.00318

GnomAD4 exome AF: 0.00139 AC: 2021 AN: 1456554 Hom.: 2 Cov.: 33 AF XY: 0.00138 AC XY: 1000 AN XY: 724256

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.00246

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000386

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.00150

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00120 AC: 182 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.00124 AC XY: 92 AN XY: 74454

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00164

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TRAPPC14-related disorder Benign:1

Jun 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.012
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

Publications

LitVar

Other links and lift over

dbSNP: rs143162409; hg19: chr7-99754343;