Genetic Variant NM_020776.3:c.538C>G (chr18-36959397-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020776.3(KIAA1328):c.538C>G(p.Leu180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,609,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KIAA1328
NM_020776.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

Publications

0 publications found

Variant links:

Genes affected

KIAA1328 (HGNC:29248): (KIAA1328)

KIAA1328 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10234594).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1328	NM_020776.3	MANE Select	c.538C>G	p.Leu180Val	missense	Exon 6 of 10	NP_065827.1	Q86T90-1
KIAA1328	NM_001353920.2		c.-594C>G		5_prime_UTR_premature_start_codon_gain	Exon 6 of 11	NP_001340849.1
KIAA1328	NM_001353918.2		c.526C>G	p.Leu176Val	missense	Exon 6 of 10	NP_001340847.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1328	ENST00000280020.10	TSL:1 MANE Select	c.538C>G	p.Leu180Val	missense	Exon 6 of 10	ENSP00000280020.5	Q86T90-1
KIAA1328	ENST00000591619.5	TSL:1	c.526C>G	p.Leu176Val	missense	Exon 6 of 11	ENSP00000465550.1	Q86T90-2
KIAA1328	ENST00000586135.1	TSL:1	c.-277+12880C>G		intron	N/A	ENSP00000467507.1	Q86T90-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000207

AC:

AN:

241588

AF XY:

0.0000230

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1457286

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724374

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33340

American (AMR)

AF:

0.00

AC:

AN:

43914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

84960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1110176

Other (OTH)

AF:

0.0000166

AC:

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68054

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.58

M_CAP

Benign

0.014

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

2.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

REVEL

Benign

0.027

Sift

Benign

0.14

Sift4G

Benign

0.43

Polyphen

0.25

Vest4

0.25

MutPred

0.10

Gain of relative solvent accessibility (P = 0.1259)

MVP

0.21

MPC

0.049

ClinPred

0.046

GERP RS

3.8

Varity_R

0.090

gMVP

0.025

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over