rs199648809

Variant names:

• chr19-47476834-C-A
• NM_007059.4:c.968G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-47476834-C-A
• chr19-47476834-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007059.4(KPTN):​c.968G>T​(p.Arg323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KPTN NM_007059.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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]

ENSG00000287896 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0667108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPTN	NM_007059.4	c.968G>T	p.Arg323Leu	missense_variant	Exon 10 of 12	ENST00000338134.8	NP_008990.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPTN	ENST00000338134.8	c.968G>T	p.Arg323Leu	missense_variant	Exon 10 of 12	1	NM_007059.4	ENSP00000337850.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430054 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.0
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.053
Sift	Benign	0.17	T
Sift4G	Uncertain	0.048	D
Polyphen		0.095	B
Vest4		0.17
MutPred		0.32		Loss of sheet (P = 0.007);
MVP		0.16
MPC		0.49
ClinPred		0.34	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-47980091;