chr1-200975592-G-C

Position:

• chr1-200975592-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001252102.2(KIF21B):​c.4521C>G​(p.Ile1507Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF21B NM_001252102.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04

Genes affected

KIF21B (HGNC:29442): (kinesin family member 21B) This gene encodes a member of the kinesin superfamily. Kinesins are ATP-dependent microtubule-based motor proteins that are involved in the intracellular transport of membranous organelles. Single nucleotide polymorphisms in this gene are associated with inflammatory bowel disease and multiple sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.4521C>G	p.Ile1507Met	missense_variant	33/35	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.4521C>G	p.Ile1507Met	missense_variant	33/35	1	NM_001252102.2	ENSP00000433808	P3
KIF21B	ENST00000422435.2	c.4521C>G	p.Ile1507Met	missense_variant	33/35	1		ENSP00000411831
KIF21B	ENST00000332129.6	c.4482C>G	p.Ile1494Met	missense_variant	32/34	1		ENSP00000328494
KIF21B	ENST00000360529.9	c.4482C>G	p.Ile1494Met	missense_variant	32/34	1		ENSP00000353724	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 27, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	.;.;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.1	.;M;.;M
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.90	P;.;.;P
Vest4		0.80
MutPred		0.60		.;Gain of disorder (P = 0.0687);.;Gain of disorder (P = 0.0687);
MVP		0.78
MPC		1.4
ClinPred		0.93	D
GERP RS		-2.2
Varity_R		0.39
gMVP		0.42

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: chr1-200944720;