3-124434374-A-C

Position:

• chr3-124434374-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001388419.1(KALRN):​c.2897A>C​(p.Glu966Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KALRN NM_001388419.1 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 9.32

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-124434374-A-C is Benign according to our data. Variant chr3-124434374-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2681344.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.2897A>C	p.Glu966Ala	missense_variant	17/60	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.2897A>C	p.Glu966Ala	missense_variant	17/60		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.1	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.85	P;P;.
Vest4		0.57
MutPred		0.58		.;Loss of ubiquitination at K962 (P = 0.0787);Loss of ubiquitination at K962 (P = 0.0787);
MVP		0.71
MPC		1.6
ClinPred		1.0	D
GERP RS		5.1
gMVP		0.55

Splicing

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: chr3-124153221;