18-36829152-C-A

Variant names:

• chr18-36829152-C-A
• rs1053006436
• NM_020776.3:c.14C>A

Variant summary

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

The NM_020776.3(KIAA1328):​c.14C>A​(p.Ala5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA1328 NM_020776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

KIAA1328 (HGNC:29248): (KIAA1328)

TPGS2 (HGNC:24561): (tubulin polyglutamylase complex subunit 2) This gene encodes a protein that is a component of the neuronal polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2012]

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=0.21645668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020776.3. 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
	KIAA1328	NM_020776.3	MANE Select	c.14C>A	p.Ala5Glu	missense	Exon 1 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001353918.2		c.14C>A	p.Ala5Glu	missense	Exon 1 of 10	NP_001340847.1
	KIAA1328	NM_001322327.2		c.-216C>A		5_prime_UTR	Exon 1 of 10	NP_001309256.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1328	ENST00000280020.10	TSL:1 MANE Select	c.14C>A	p.Ala5Glu	missense	Exon 1 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000590617.5	TSL:1	n.14C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000467248.1	K7EP66
	KIAA1328	ENST00000908902.1		c.14C>A	p.Ala5Glu	missense	Exon 1 of 11	ENSP00000578961.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381376 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681228

African (AFR) AF: 0.00 AC: 0 AN: 29560

American (AMR) AF: 0.00 AC: 0 AN: 34840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24614

East Asian (EAS) AF: 0.00 AC: 0 AN: 34210

South Asian (SAS) AF: 0.00 AC: 0 AN: 77706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5160

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074168

Other (OTH) AF: 0.00 AC: 0 AN: 57424

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74272

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.053
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.015	B
Vest4		0.32
MutPred		0.094		Loss of catalytic residue at D3 (P = 0.082)
MVP		0.28
MPC		0.054
ClinPred		0.89	D
GERP RS		3.2
PromoterAI		-0.017	Neutral
Varity_R		0.27
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1053006436; hg19: chr18-34409115;