dbSNP rs1062749: KALRN:p.Gly1590Glu (chr3-124492819-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001388419.1(KALRN):c.4769G>A(p.Gly1590Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

KALRN
NM_001388419.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Publications

1 publications found

Variant links:

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

KALRN links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388419.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KALRN	NM_001388419.1	MANE Select	c.4769G>A	p.Gly1590Glu	missense	Exon 32 of 60	NP_001375348.1
KALRN	NM_001024660.5		c.4763G>A	p.Gly1588Glu	missense	Exon 32 of 60	NP_001019831.2
KALRN	NM_001322988.2		c.4763G>A	p.Gly1588Glu	missense	Exon 32 of 49	NP_001309917.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KALRN	ENST00000682506.1	MANE Select	c.4769G>A	p.Gly1590Glu	missense	Exon 32 of 60	ENSP00000508359.1
KALRN	ENST00000240874.7	TSL:1	c.4763G>A	p.Gly1588Glu	missense	Exon 32 of 34	ENSP00000240874.3
KALRN	ENST00000460856.5	TSL:1	c.4736G>A	p.Gly1579Glu	missense	Exon 32 of 34	ENSP00000418611.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.000156

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.5

PhyloP100

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.010

Polyphen

0.76

Vest4

0.62

MutPred

0.43

Gain of solvent accessibility (P = 0.0281)

MVP

0.85

MPC

1.6

ClinPred

0.98

GERP RS

5.5

gMVP

0.79

Mutation Taster

=56/44

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over