dbSNP rs61743291: KPTN:p.Pro168Pro (chr19-47480979-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007059.4(KPTN):c.504G>A(p.Pro168Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,601,960 control chromosomes in the GnomAD database, including 648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 74 hom., cov: 31)

Exomes 𝑓: 0.025 ( 574 hom. )

Consequence

KPTN
NM_007059.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.74

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-47480979-C-T is Benign according to our data. Variant chr19-47480979-C-T is described in ClinVar as [Benign]. Clinvar id is 474857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.74 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3257/152246) while in subpopulation NFE AF= 0.0296 (2012/68016). AF 95% confidence interval is 0.0285. There are 74 homozygotes in gnomad4. There are 1694 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPTN	NM_007059.4 link	c.504G>A	p.Pro168Pro	synonymous_variant	Exon 5 of 12	ENST00000338134.8	NP_008990.2	Q9Y664-1A0A384NLB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPTN	ENST00000338134.8 link	c.504G>A	p.Pro168Pro	synonymous_variant	Exon 5 of 12	1	NM_007059.4	ENSP00000337850.2		Q9Y664-1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3260

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0725

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0218

AC:

4900

AN:

225106

Hom.:

101

AF XY:

0.0211

AC XY:

2585

AN XY:

122268

show subpopulations

Gnomad AFR exome

AF:

0.00426

Gnomad AMR exome

AF:

0.00798

Gnomad ASJ exome

AF:

0.00446

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00368

Gnomad FIN exome

AF:

0.0752

Gnomad NFE exome

AF:

0.0285

Gnomad OTH exome

AF:

0.0174

GnomAD4 exome

AF:

0.0251

AC:

36401

AN:

1449714

Hom.:

574

Cov.:

AF XY:

0.0245

AC XY:

17634

AN XY:

720186

show subpopulations

Gnomad4 AFR exome

AF:

0.00343

Gnomad4 AMR exome

AF:

0.00835

Gnomad4 ASJ exome

AF:

0.00548

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00445

Gnomad4 FIN exome

AF:

0.0690

Gnomad4 NFE exome

AF:

0.0276

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0214

AC:

3257

AN:

152246

Hom.:

Cov.:

AF XY:

0.0228

AC XY:

1694

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00424

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0725

Gnomad4 NFE

AF:

0.0296

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Macrocephaly-developmental delay syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KPTN-related disorder

Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.25

DANN

Benign

0.40

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