18-36829161-C-A

Variant names:

• chr18-36829161-C-A
• rs1203596631
• NM_020776.3:c.23C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020776.3(KIAA1328):​c.23C>A​(p.Ser8Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. S8F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KIAA1328 NM_020776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36821654).

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.23C>A	p.Ser8Tyr	missense	Exon 1 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001353918.2		c.23C>A	p.Ser8Tyr	missense	Exon 1 of 10	NP_001340847.1
	KIAA1328	NM_001322327.2		c.-207C>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.23C>A	p.Ser8Tyr	missense	Exon 1 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000590617.5	TSL:1	n.23C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000467248.1	K7EP66
	KIAA1328	ENST00000908902.1		c.23C>A	p.Ser8Tyr	missense	Exon 1 of 11	ENSP00000578961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 123404 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381470 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681324

African (AFR) AF: 0.00 AC: 0 AN: 29650

American (AMR) AF: 0.00 AC: 0 AN: 34884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24646

East Asian (EAS) AF: 0.00 AC: 0 AN: 34302

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074410

Other (OTH) AF: 0.00 AC: 0 AN: 57468

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	0.056
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.040
Sift	Uncertain	0.025	D
Sift4G	Benign	0.065	T
Polyphen		0.82	P
Vest4		0.44
MutPred		0.21		Loss of disorder (P = 0.0023)
MVP		0.38
MPC		0.31
ClinPred		0.81	D
GERP RS		3.5
PromoterAI		-0.081	Neutral
Varity_R		0.085
gMVP		0.061
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1203596631; hg19: chr18-34409124;