Genetic Variant KIAA1671:p.Asp328Gly (chr22-25028982-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145206.2(KIAA1671):c.983A>G(p.Asp328Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,533,228 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

KIAA1671
NM_001145206.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.838

Publications

0 publications found

Variant links:

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

KIAA1671 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037682503).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145206.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1671	NM_001145206.2	MANE Select	c.983A>G	p.Asp328Gly	missense	Exon 3 of 13	NP_001138678.1	Q9BY89-1
KIAA1671	NM_001386930.1		c.983A>G	p.Asp328Gly	missense	Exon 3 of 12	NP_001373859.1
KIAA1671	NM_001386932.1		c.983A>G	p.Asp328Gly	missense	Exon 3 of 13	NP_001373861.1	Q9BY89-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1671	ENST00000358431.8	TSL:1 MANE Select	c.983A>G	p.Asp328Gly	missense	Exon 3 of 13	ENSP00000351207.3	Q9BY89-1
KIAA1671	ENST00000406486.8	TSL:5	c.983A>G	p.Asp328Gly	missense	Exon 4 of 14	ENSP00000385152.3	Q9BY89-1
KIAA1671	ENST00000910712.1		c.983A>G	p.Asp328Gly	missense	Exon 4 of 14	ENSP00000580771.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000138

AC:

191

AN:

1380880

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

129

AN XY:

679690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30832

American (AMR)

AF:

0.0000311

AC:

AN:

32148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23820

East Asian (EAS)

AF:

0.00

AC:

AN:

35540

South Asian (SAS)

AF:

0.00223

AC:

170

AN:

76396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48790

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00000467

AC:

AN:

1070700

Other (OTH)

AF:

0.000245

AC:

AN:

57064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000591

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41592

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00166

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.30

M_CAP

Benign

0.0086

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.84

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.46

REVEL

Benign

0.026

Sift

Benign

0.15

Sift4G

Uncertain

0.055

Polyphen

0.0

Vest4

0.10

MutPred

0.27

Loss of stability (P = 0.0031)

MVP

0.088

ClinPred

0.049

GERP RS

0.63

Varity_R

0.048

gMVP

0.036

Mutation Taster

=99/1

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