Variant rs1046273 details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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]

KPTN links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

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

Synonymous conserved (PhyloP=0.629 with no splicing effect.

BA1

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	Protein	UniProt
KPTN	NM_007059.4 linkuse as main transcript	c.1245G>A	p.Arg415=	synonymous_variant	12/12	ENST00000338134.8	NP_008990.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPTN	ENST00000338134.8 linkuse as main transcript	c.1245G>A	p.Arg415=	synonymous_variant	12/12	1	NM_007059.4	ENSP00000337850	P1	Q9Y664-1
	ENST00000669287.1 linkuse as main transcript	n.69-980C>T		intron_variant, non_coding_transcript_variant
KPTN	ENST00000600551.1 linkuse as main transcript	n.136G>A		non_coding_transcript_exon_variant	2/2	5
KPTN	ENST00000594208.5 linkuse as main transcript	c.*879G>A		3_prime_UTR_variant, NMD_transcript_variant	13/13	2		ENSP00000470364

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2667

AN:

152230

Hom.:

Cov.:

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.:

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

AF:

0.0176

AC:

2676

AN:

152348

Hom.:

Cov.:

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.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0213

EpiControl

AF:

0.0167

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Macrocephaly-developmental delay syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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.

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