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GeneBe

19-47475482-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_007059.4(KPTN):c.1245G>A(p.Arg415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,613,516 control chromosomes in the GnomAD database, including 547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 46 hom., cov: 31)
Exomes 𝑓: 0.022 ( 501 hom. )

Consequence

KPTN
NM_007059.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.629
Variant links:
Genes affected
KPTN (HGNC:6404): (kaptin, actin binding protein) This gene encodes a filamentous-actin-associated protein, which is involved in actin dynamics and plays an important role in neuromorphogenesis. This protein is part of the KICSTOR protein complex that localizes to lysosomes. Mutations in this gene result in an autosomal recessive form of intellectual disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-47475482-C-T is Benign according to our data. Variant chr19-47475482-C-T is described in ClinVar as [Benign]. Clinvar id is 474856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.629 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KPTNNM_007059.4 linkuse as main transcriptc.1245G>A p.Arg415= synonymous_variant 12/12 ENST00000338134.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KPTNENST00000338134.8 linkuse as main transcriptc.1245G>A p.Arg415= synonymous_variant 12/121 NM_007059.4 P1Q9Y664-1
ENST00000669287.1 linkuse as main transcriptn.69-980C>T intron_variant, non_coding_transcript_variant
KPTNENST00000600551.1 linkuse as main transcriptn.136G>A non_coding_transcript_exon_variant 2/25
KPTNENST00000594208.5 linkuse as main transcriptc.*879G>A 3_prime_UTR_variant, NMD_transcript_variant 13/132

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0175
AC:
2667
AN:
152230
Hom.:
44
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00376
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.0508
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0240
Gnomad FIN
AF:
0.00781
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0217
Gnomad OTH
AF:
0.0196
GnomAD3 exomes
AF:
0.0244
AC:
6070
AN:
248588
Hom.:
145
AF XY:
0.0237
AC XY:
3201
AN XY:
134942
show subpopulations
Gnomad AFR exome
AF:
0.00318
Gnomad AMR exome
AF:
0.0684
Gnomad ASJ exome
AF:
0.00279
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0273
Gnomad FIN exome
AF:
0.0129
Gnomad NFE exome
AF:
0.0213
Gnomad OTH exome
AF:
0.0215
GnomAD4 exome
AF:
0.0216
AC:
31554
AN:
1461168
Hom.:
501
Cov.:
31
AF XY:
0.0217
AC XY:
15791
AN XY:
726870
show subpopulations
Gnomad4 AFR exome
AF:
0.00302
Gnomad4 AMR exome
AF:
0.0659
Gnomad4 ASJ exome
AF:
0.00287
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0266
Gnomad4 FIN exome
AF:
0.0136
Gnomad4 NFE exome
AF:
0.0217
Gnomad4 OTH exome
AF:
0.0198
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0176
AC:
2676
AN:
152348
Hom.:
46
Cov.:
31
AF XY:
0.0181
AC XY:
1352
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.00375
Gnomad4 AMR
AF:
0.0514
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0240
Gnomad4 FIN
AF:
0.00781
Gnomad4 NFE
AF:
0.0217
Gnomad4 OTH
AF:
0.0194
Alfa
AF:
0.0180
Hom.:
11
Bravo
AF:
0.0195
Asia WGS
AF:
0.00779
AC:
27
AN:
3478
EpiCase
AF:
0.0213
EpiControl
AF:
0.0167

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Macrocephaly-developmental delay syndrome Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
7.2
Dann
Benign
0.68

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: rs1046273; hg19: chr19-47978739; COSMIC: COSV52639435; COSMIC: COSV52639435; API