18-36829157-C-A

Variant names:

• chr18-36829157-C-A
• rs769042456
• NM_020776.3:c.19C>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.19C>A​(p.Pro7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,810 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. P7S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIAA1328 NM_020776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• 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=0.31708354).

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.19C>A	p.Pro7Thr	missense	Exon 1 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001353918.2		c.19C>A	p.Pro7Thr	missense	Exon 1 of 10	NP_001340847.1
	KIAA1328	NM_001322327.2		c.-211C>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.19C>A	p.Pro7Thr	missense	Exon 1 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000590617.5	TSL:1	n.19C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000467248.1	K7EP66
	KIAA1328	ENST00000908902.1		c.19C>A	p.Pro7Thr	missense	Exon 1 of 11	ENSP00000578961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000163 AC: 2 AN: 122362 AF XY: 0.0000298

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: 0.0000227

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1380810 Hom.: 0 Cov.: 31 AF XY: 0.00000294 AC XY: 2 AN XY: 680954

African (AFR) AF: 0.00 AC: 0 AN: 29578

American (AMR) AF: 0.00 AC: 0 AN: 34836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24640

East Asian (EAS) AF: 0.0000292 AC: 1 AN: 34210

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074208

Other (OTH) AF: 0.00 AC: 0 AN: 57438

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.61
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.077
Sift	Benign	0.21	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.21		Gain of phosphorylation at P7 (P = 0.0108)
MVP		0.30
MPC		0.31
ClinPred		0.63	D
GERP RS		2.5
PromoterAI		-0.082	Neutral
Varity_R		0.048
gMVP		0.049
Mutation Taster		=86/14	polymorphism

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: rs769042456; hg19: chr18-34409120; COSMIC: COSV99694343; COSMIC: COSV99694343;