19-47475414-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007059.4(KPTN):c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,611,002 control chromosomes in the GnomAD database, including 14,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1707 hom., cov: 31)
  • Exomes 𝑓: 0.12 (12599 hom.)
• Consequence: KPTN NM_007059.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.521

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 19-47475414-G-A is Benign according to our data. Variant chr19-47475414-G-A is described in ClinVar as [Benign]. Clinvar id is 1179592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPTN	NM_007059.4	c.*2C>T		3_prime_UTR_variant	12/12	ENST00000338134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPTN	ENST00000338134.8	c.*2C>T		3_prime_UTR_variant	12/12	1	NM_007059.4	P1
	ENST00000669287.1	n.69-1048G>A		intron_variant, non_coding_transcript_variant
KPTN	ENST00000600551.1	n.204C>T		non_coding_transcript_exon_variant	2/2	5
KPTN	ENST00000594208.5	c.*947C>T		3_prime_UTR_variant, NMD_transcript_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22005 AN: 151992 Hom.: 1702 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.150 AC: 36889 AN: 246172 Hom.: 3256 AF XY: 0.144 AC XY: 19286 AN XY: 133776

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.0540

Gnomad EAS exome AF: 0.227

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.124 AC: 181377 AN: 1458892 Hom.: 12599 Cov.: 31 AF XY: 0.124 AC XY: 90006 AN XY: 725670

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.0553

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.145 AC: 22055 AN: 152110 Hom.: 1707 Cov.: 31 AF XY: 0.149 AC XY: 11047 AN XY: 74360

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.142

Alfa AF: 0.114 Hom.: 2222

Bravo AF: 0.150

Asia WGS AF: 0.189 AC: 659 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.8
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs2272295; hg19: chr19-47978671;