18-36829161-C-G

Variant names:

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

Variant summary

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

The NM_001322327.2(KIAA1328):​c.-207C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,381,470 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: KIAA1328 NM_001322327.2 5_prime_UTR_premature_start_codon_gain
• 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=0.3573897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322327.2. 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>G	p.Ser8Cys	missense	Exon 1 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001322327.2		c.-207C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001309256.1
	KIAA1328	NM_001353919.2		c.-207C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001340848.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1328	ENST00000280020.10	TSL:1 MANE Select	c.23C>G	p.Ser8Cys	missense	Exon 1 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000590617.5	TSL:1	n.23C>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000467248.1	K7EP66
	KIAA1328	ENST00000908902.1		c.23C>G	p.Ser8Cys	missense	Exon 1 of 11	ENSP00000578961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1381470 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681324

African (AFR) AF: 0.0000337 AC: 1 AN: 29650

American (AMR) AF: 0.0000287 AC: 1 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: 0.00 AC: 0 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: 0.00000186 AC: 2 AN: 1074410

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.082
Sift	Benign	0.055	T
Sift4G	Benign	0.093	T
Polyphen		0.99	D
Vest4		0.39
MutPred		0.22		Loss of glycosylation at S8 (P = 0.003)
MVP		0.41
MPC		0.31
ClinPred		0.82	D
GERP RS		3.5
PromoterAI		-0.098	Neutral
Varity_R		0.11
gMVP		0.055

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

Other links and lift over

dbSNP: rs1203596631; hg19: chr18-34409124;