1-200975513-G-C

Variant names:

• chr1-200975513-G-C
• NM_001252102.2:c.4600C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001252102.2(KIF21B):​c.4600C>G​(p.Gln1534Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 7.97

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32679206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.4600C>G	p.Gln1534Glu	missense_variant	Exon 33 of 35	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.4600C>G	p.Gln1534Glu	missense_variant	Exon 33 of 35	1	NM_001252102.2	ENSP00000433808.1
KIF21B	ENST00000422435.2	c.4600C>G	p.Gln1534Glu	missense_variant	Exon 33 of 35	1		ENSP00000411831.2
KIF21B	ENST00000332129.6	c.4561C>G	p.Gln1521Glu	missense_variant	Exon 32 of 34	1		ENSP00000328494.2
KIF21B	ENST00000360529.9	c.4561C>G	p.Gln1521Glu	missense_variant	Exon 32 of 34	1		ENSP00000353724.5

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 specified Uncertain:1

Sep 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4561C>G (p.Q1521E) alteration is located in exon 32 (coding exon 32) of the KIF21B gene. This alteration results from a C to G substitution at nucleotide position 4561, causing the glutamine (Q) at amino acid position 1521 to be replaced by a glutamic acid (E). 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	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	.;.;.;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.91	.;L;.;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.71	P;.;.;B
Vest4		0.52
MutPred		0.32		.;Gain of loop (P = 0.1069);.;Gain of loop (P = 0.1069);
MVP		0.42
MPC		1.1
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.51

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: chr1-200944641;