19-8333116-G-T

Position:

• chr19-8333116-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198471.3(KANK3):​c.1834C>A​(p.Leu612Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KANK3 NM_198471.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

Genes affected

KANK3 (HGNC:24796): (KN motif and ankyrin repeat domains 3) Predicted to be involved in negative regulation of actin filament polymerization. Predicted to be active in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK3	NM_198471.3	c.1834C>A	p.Leu612Met	missense_variant	7/11	ENST00000330915.7	NP_940873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK3	ENST00000330915.7	c.1834C>A	p.Leu612Met	missense_variant	7/11	1	NM_198471.3	ENSP00000328923.2
KANK3	ENST00000593649.5	c.1834C>A	p.Leu612Met	missense_variant	7/11	1		ENSP00000470728.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.1834C>A (p.L612M) alteration is located in exon 7 (coding exon 6) of the KANK3 gene. This alteration results from a C to A substitution at nucleotide position 1834, causing the leucine (L) at amino acid position 612 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.0028	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	.;T;.
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;T;T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N;.;.
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.57
MutPred		0.54		Gain of MoRF binding (P = 0.0794);Gain of MoRF binding (P = 0.0794);.;
MVP		0.74
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.46

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: chr19-8398000;