7-138918536-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164665.2(KIAA1549):c.1090A>G(p.Thr364Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,426 control chromosomes in the GnomAD database, including 38,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 7262 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31012 hom. )

Consequence

KIAA1549
NM_001164665.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.44

Variant links:

Genes affected

KIAA1549 (HGNC:22219): (KIAA1549) The protein encoded by this gene belongs to the UPF0606 family. This gene has been found to be fused to the BRAF oncogene in many cases of pilocytic astrocytoma. The fusion results from 2Mb tandem duplications at 7q34. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

KIAA1549 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0390105E-4).

BP6

Variant 7-138918536-T-C is Benign according to our data. Variant chr7-138918536-T-C is described in ClinVar as [Benign]. Clinvar id is 1166981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2 link	c.1090A>G	p.Thr364Ala	missense_variant	Exon 2 of 20	ENST00000422774.2	NP_001158137.1	Q9HCM3-1
KIAA1549	NM_020910.3 link	c.1090A>G	p.Thr364Ala	missense_variant	Exon 2 of 20		NP_065961.2	Q9HCM3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2 link	c.1090A>G	p.Thr364Ala	missense_variant	Exon 2 of 20	1	NM_001164665.2	ENSP00000416040.2		Q9HCM3-1
KIAA1549	ENST00000440172.5 link	c.1090A>G	p.Thr364Ala	missense_variant	Exon 2 of 20	1		ENSP00000406661.1		Q9HCM3-2

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41307

AN:

151650

Hom.:

7242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.208

AC:

51836

AN:

249292

Hom.:

6481

AF XY:

0.210

AC XY:

28369

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.196

AC:

286717

AN:

1461660

Hom.:

31012

Cov.:

AF XY:

0.198

AC XY:

143961

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.273

AC:

41378

AN:

151766

Hom.:

7262

Cov.:

AF XY:

0.272

AC XY:

20172

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.506

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.312

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.181

Hom.:

3869

Bravo

AF:

0.280

TwinsUK

AF:

0.193

AC:

715

ALSPAC

AF:

0.176

AC:

678

ESP6500AA

AF:

0.474

AC:

2043

ESP6500EA

AF:

0.183

AC:

1555

ExAC

AF:

0.218

AC:

26392

Asia WGS

AF:

0.249

AC:

868

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.186

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 86

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0060

DANN

Benign

0.81

DEOGEN2

Benign

0.0092

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.00070

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.0080

Sift

Benign

0.25

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0040

B;B

Vest4

0.018

MPC

0.098

ClinPred

0.0071

GERP RS

-2.7

Varity_R

0.027

gMVP

0.20

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