18-36959400-T-C

Variant names:

• chr18-36959400-T-C
• rs749804365
• NM_020776.3:c.541T>C

Variant summary

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

The NM_020776.3(KIAA1328):​c.541T>C​(p.Ser181Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S181A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1328 NM_020776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• Publications: 0 publications found

Genes affected

KIAA1328 (HGNC:29248): (KIAA1328)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.541T>C	p.Ser181Pro	missense	Exon 6 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001353918.2		c.529T>C	p.Ser177Pro	missense	Exon 6 of 10	NP_001340847.1
	KIAA1328	NM_001322327.2		c.217T>C	p.Ser73Pro	missense	Exon 5 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.541T>C	p.Ser181Pro	missense	Exon 6 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000591619.5	TSL:1	c.529T>C	p.Ser177Pro	missense	Exon 6 of 11	ENSP00000465550.1	Q86T90-2
	KIAA1328	ENST00000586135.1	TSL:1	c.-277+12883T>C		intron	N/A	ENSP00000467507.1	Q86T90-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.15		Loss of phosphorylation at S181 (P = 0.0245)
MVP		0.61
MPC		0.34
ClinPred		0.91	D
GERP RS		5.6
Varity_R		0.63
gMVP		0.22
Mutation Taster		=90/10	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: rs749804365; hg19: chr18-34539363;