NM_020776.3:c.19C>T

Variant names:

• chr18-36829157-C-T
• rs769042456
• NM_020776.3:c.19C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020776.3(KIAA1328):​c.19C>T​(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,532,886 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (3 hom.)
• Consequence: KIAA1328 NM_020776.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004609406).
• BP6: Variant 18-36829157-C-T is Benign according to our data. Variant chr18-36829157-C-T is described in ClinVar as Benign. ClinVar VariationId is 735154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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>T	p.Pro7Ser	missense	Exon 1 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001353918.2		c.19C>T	p.Pro7Ser	missense	Exon 1 of 10	NP_001340847.1
	KIAA1328	NM_001322327.2		c.-211C>T		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>T	p.Pro7Ser	missense	Exon 1 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000590617.5	TSL:1	n.19C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000467248.1	K7EP66
	KIAA1328	ENST00000908902.1		c.19C>T	p.Pro7Ser	missense	Exon 1 of 11	ENSP00000578961.1

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00101 AC: 123 AN: 122362 AF XY: 0.00124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0150

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000182

Gnomad OTH exome AF: 0.000546

GnomAD4 exome AF: 0.000365 AC: 504 AN: 1380808 Hom.: 3 Cov.: 31 AF XY: 0.000388 AC XY: 264 AN XY: 680954

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

American (AMR) AF: 0.0000287 AC: 1 AN: 34836

Ashkenazi Jewish (ASJ) AF: 0.0152 AC: 374 AN: 24638

East Asian (EAS) AF: 0.00 AC: 0 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: 0.000193 AC: 1 AN: 5178

European-Non Finnish (NFE) AF: 0.0000670 AC: 72 AN: 1074208

Other (OTH) AF: 0.000958 AC: 55 AN: 57438

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26 AN XY: 74292

African (AFR) AF: 0.0000724 AC: 3 AN: 41430

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67970

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.000397

ExAC AF: 0.000528 AC: 29

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.61
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.078
Sift	Benign	0.52	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.27
MVP		0.30
MPC		0.26
ClinPred		0.15	T
GERP RS		2.5
PromoterAI		-0.0091	Neutral
Varity_R		0.033
gMVP		0.050
Mutation Taster		=88/12	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;