rs758438766

Variant names:

• chr19-47479873-C-A
• rs758438766
• NM_007059.4:c.777G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-47479873-C-A
• chr19-47479873-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007059.4(KPTN):​c.777G>T​(p.Ser259Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S259S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KPTN NM_007059.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• macrocephaly-developmental delay syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPTN	NM_007059.4	MANE Select	c.777G>T	p.Ser259Ser	synonymous	Exon 8 of 12	NP_008990.2	Q9Y664-1
	KPTN	NM_001291296.2		c.609G>T	p.Ser203Ser	synonymous	Exon 6 of 10	NP_001278225.1
	KPTN	NR_111923.2		n.923G>T		non_coding_transcript_exon	Exon 9 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPTN	ENST00000338134.8	TSL:1 MANE Select	c.777G>T	p.Ser259Ser	synonymous	Exon 8 of 12	ENSP00000337850.2	Q9Y664-1
	KPTN	ENST00000914958.1		c.748G>T	p.Gly250Cys	missense	Exon 8 of 11	ENSP00000585017.1
	KPTN	ENST00000914957.1		c.777G>T	p.Ser259Ser	synonymous	Exon 8 of 12	ENSP00000585016.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248384 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.017
DANN	Benign	0.88
PhyloP100		-2.2

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

Other links and lift over

dbSNP: rs758438766; hg19: chr19-47983130;