Variant 20-38213221-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001029864.2(KIAA1755):c.3424T>G(p.Ser1142Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,613,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

KIAA1755
NM_001029864.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

Variant links:

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

KIAA1755 links:

KIAA1755 (HGNC:):

KIAA1755 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027007729).

BP6

Variant 20-38213221-A-C is Benign according to our data. Variant chr20-38213221-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2385501.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1755	NM_001029864.2 linkuse as main transcript	c.3424T>G	p.Ser1142Ala	missense_variant	14/14	ENST00000279024.9	NP_001025035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIAA1755	ENST00000279024.9 linkuse as main transcript	c.3424T>G	p.Ser1142Ala	missense_variant	14/14	5	NM_001029864.2	ENSP00000279024.4	Q5JYT7
KIAA1755	ENST00000460881.5 linkuse as main transcript	n.1600T>G		non_coding_transcript_exon_variant	3/3	1
KIAA1755	ENST00000487506.1 linkuse as main transcript	n.1376T>G		non_coding_transcript_exon_variant	2/2	1
KIAA1755	ENST00000484362.1 linkuse as main transcript	n.1703T>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000560

AC:

AN:

249926

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000229

AC:

335

AN:

1461006

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.047

DANN

Benign

0.18

DEOGEN2

Benign

0.00038

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.15

M_CAP

Benign

0.0028

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.25

PROVEAN

Benign

0.11

REVEL

Benign

0.010

Sift

Benign

0.86

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.044

MVP

0.055

MPC

0.033

ClinPred

0.022

GERP RS

-6.5

Varity_R

0.033

gMVP

0.064

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over