8-140360188-G-T

Variant names:

• chr8-140360188-G-T
• NM_001160372.4:c.1357C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001160372.4(TRAPPC9):​c.1357C>A​(p.His453Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.70

Genes affected

TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.1357C>A	p.His453Asn	missense_variant	Exon 9 of 23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.1357C>A	p.His453Asn	missense_variant	Exon 9 of 23	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000520857.5	c.886C>A	p.His296Asn	missense_variant	Exon 7 of 21	1		ENSP00000430116.1
TRAPPC9	ENST00000648948.2	c.1357C>A	p.His453Asn	missense_variant	Exon 9 of 23			ENSP00000498020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T;T;.;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L;L;.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	.;N;N;.
REVEL	Benign	0.28
Sift	Benign	0.41	.;T;T;.
Sift4G	Benign	0.17	.;T;T;.
Polyphen		0.96	D;D;P;D
Vest4		0.67, 0.69
MutPred		0.36		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);.;Gain of relative solvent accessibility (P = 0.0082);
MVP		0.24
MPC		1.0
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.34
gMVP		0.54

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-141370287;