7-100156720-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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]

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

Our verdict: Benign. The variant received -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 VariationId is 3044098.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.994-4G>A		splice_region intron	N/A	NP_060745.3
	TRAPPC14	NM_001303470.2		c.187-4G>A		splice_region intron	N/A	NP_001290399.1	B3KNS5
	MIR4658	NR_039802.1		n.-51G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC14	ENST00000316937.8	TSL:1 MANE Select	c.994-4G>A		splice_region intron	N/A	ENSP00000324741.3	Q8WVR3-1
	TRAPPC14	ENST00000950372.1		c.994-4G>A		splice_region intron	N/A	ENSP00000620431.1
	TRAPPC14	ENST00000950373.1		c.994-4G>A		splice_region intron	N/A	ENSP00000620432.1

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

GnomAD2 exomes AF: 0.00132 AC: 325 AN: 245348 AF XY: 0.00133

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 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

African (AFR) AF: 0.000150 AC: 5 AN: 33416

American (AMR) AF: 0.00353 AC: 156 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.00246 AC: 63 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000386 AC: 33 AN: 85412

European-Finnish (FIN) AF: 0.000132 AC: 7 AN: 53114

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5742

European-Non Finnish (NFE) AF: 0.00150 AC: 1666 AN: 1109254

Other (OTH) AF: 0.00146 AC: 88 AN: 60142

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

African (AFR) AF: 0.000361 AC: 15 AN: 41560

American (AMR) AF: 0.00399 AC: 61 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00135 AC: 92 AN: 68002

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00164

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TRAPPC14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.57
PhyloP100		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs143162409; hg19: chr7-99754343;