chr3-42685942-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000287777.5(KLHL40):ā€‹c.324A>Gā€‹(p.Ala108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,611,720 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.033 ( 277 hom., cov: 33)
Exomes š‘“: 0.0037 ( 241 hom. )

Consequence

KLHL40
ENST00000287777.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 1.00
Variant links:
Genes affected
KLHL40 (HGNC:30372): (kelch like family member 40) This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 3-42685942-A-G is Benign according to our data. Variant chr3-42685942-A-G is described in ClinVar as [Benign]. Clinvar id is 262644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLHL40NM_152393.4 linkuse as main transcriptc.324A>G p.Ala108= synonymous_variant 1/6 ENST00000287777.5 NP_689606.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLHL40ENST00000287777.5 linkuse as main transcriptc.324A>G p.Ala108= synonymous_variant 1/61 NM_152393.4 ENSP00000287777 P1Q2TBA0-1

Frequencies

GnomAD3 genomes
AF:
0.0333
AC:
5063
AN:
152102
Hom.:
280
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.115
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0141
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.0254
GnomAD3 exomes
AF:
0.00937
AC:
2330
AN:
248744
Hom.:
126
AF XY:
0.00681
AC XY:
919
AN XY:
134882
show subpopulations
Gnomad AFR exome
AF:
0.117
Gnomad AMR exome
AF:
0.00912
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.0000497
Gnomad NFE exome
AF:
0.000820
Gnomad OTH exome
AF:
0.00903
GnomAD4 exome
AF:
0.00372
AC:
5432
AN:
1459500
Hom.:
241
Cov.:
30
AF XY:
0.00324
AC XY:
2351
AN XY:
726198
show subpopulations
Gnomad4 AFR exome
AF:
0.117
Gnomad4 AMR exome
AF:
0.00999
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.0000978
Gnomad4 NFE exome
AF:
0.000429
Gnomad4 OTH exome
AF:
0.00840
GnomAD4 genome
AF:
0.0333
AC:
5067
AN:
152220
Hom.:
277
Cov.:
33
AF XY:
0.0322
AC XY:
2395
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.114
Gnomad4 AMR
AF:
0.0141
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000632
Gnomad4 OTH
AF:
0.0251
Alfa
AF:
0.0131
Hom.:
43
Bravo
AF:
0.0382
Asia WGS
AF:
0.00722
AC:
25
AN:
3478
EpiCase
AF:
0.000872
EpiControl
AF:
0.00113

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 18, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsFeb 25, 2019- -
Nemaline myopathy 8 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
9.4
DANN
Benign
0.64

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.

Other links and lift over

dbSNP: rs35033264; hg19: chr3-42727434; API