Variant 19-47476679-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007059.4(KPTN):c.1035G>A(p.Ser345Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 1,612,636 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00073 ( 2 hom. )

Consequence

KPTN
NM_007059.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.33

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:

ENSG00000287896 (HGNC:):

ENSG00000287896 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-47476679-C-T is Benign according to our data. Variant chr19-47476679-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-47476679-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.33 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPTN	NM_007059.4 linkuse as main transcript	c.1035G>A	p.Ser345Ser	synonymous_variant	11/12	ENST00000338134.8	NP_008990.2	Q9Y664-1A0A384NLB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KPTN	ENST00000338134.8 linkuse as main transcript	c.1035G>A	p.Ser345Ser	synonymous_variant	11/12	1	NM_007059.4	ENSP00000337850.2	Q9Y664-1
KPTN	ENST00000594208.5 linkuse as main transcript	n.*669G>A		non_coding_transcript_exon_variant	12/13	2		ENSP00000470364.1	M0QZ83
ENSG00000287896	ENST00000669287.1 linkuse as main transcript	n.286C>T		non_coding_transcript_exon_variant	2/2
KPTN	ENST00000594208.5 linkuse as main transcript	n.*669G>A		3_prime_UTR_variant	12/13	2		ENSP00000470364.1	M0QZ83

Frequencies

GnomAD3 genomes

AF:

0.000468

AC:

AN:

151622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000854

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000522

AC:

128

AN:

245090

Hom.:

AF XY:

0.000509

AC XY:

AN XY:

133468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.0000476

Gnomad NFE exome

AF:

0.000991

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000734

AC:

1073

AN:

1460896

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

535

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000359

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000894

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000468

AC:

AN:

151740

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000854

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.000704

Hom.:

Bravo

AF:

0.000484

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 09, 2016

- -

Macrocephaly-developmental delay syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 16, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

KPTN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.38

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