chr1-200975575-T-A

Position:

• chr1-200975575-T-A

Variant summary

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

The NM_001252102.2(KIF21B):​c.4538A>T​(p.Gln1513Leu) 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: 32)
• Consequence: KIF21B NM_001252102.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF21B	NM_001252102.2	c.4538A>T	p.Gln1513Leu	missense_variant	33/35	ENST00000461742.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF21B	ENST00000461742.7	c.4538A>T	p.Gln1513Leu	missense_variant	33/35	1	NM_001252102.2	P3
KIF21B	ENST00000422435.2	c.4538A>T	p.Gln1513Leu	missense_variant	33/35	1
KIF21B	ENST00000332129.6	c.4499A>T	p.Gln1500Leu	missense_variant	32/34	1
KIF21B	ENST00000360529.9	c.4499A>T	p.Gln1500Leu	missense_variant	32/34	1		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

Jan 25, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;.;.;T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;D;T;D
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.32	.;N;.;N
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.40	T;T;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.30	B;.;.;B
Vest4		0.73
MutPred		0.54		.;Loss of catalytic residue at Q1513 (P = 0.0803);.;Loss of catalytic residue at Q1513 (P = 0.0803);
MVP		0.47
MPC		0.93
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.21
gMVP		0.35

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: chr1-200944703;