1-200976828-G-T

Variant names:

• chr1-200976828-G-T
• NM_001252102.2:c.4391C>A

Variant summary

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

The NM_001252102.2(KIF21B):​c.4391C>A​(p.Thr1464Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1464M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIF21B NM_001252102.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06

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 rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.4391C>A	p.Thr1464Lys	missense_variant	Exon 32 of 35	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.4391C>A	p.Thr1464Lys	missense_variant	Exon 32 of 35	1	NM_001252102.2	ENSP00000433808.1
KIF21B	ENST00000422435.2	c.4391C>A	p.Thr1464Lys	missense_variant	Exon 32 of 35	1		ENSP00000411831.2
KIF21B	ENST00000332129.6	c.4352C>A	p.Thr1451Lys	missense_variant	Exon 31 of 34	1		ENSP00000328494.2
KIF21B	ENST00000360529.9	c.4352C>A	p.Thr1451Lys	missense_variant	Exon 31 of 34	1		ENSP00000353724.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461400 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726950

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.046	.;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	.;M;.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.91	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.21	B;.;.;B
Vest4		0.71
MutPred		0.45		.;Gain of ubiquitination at T1464 (P = 0.0128);.;Gain of ubiquitination at T1464 (P = 0.0128);
MVP		0.56
MPC		1.3
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.073
gMVP		0.36

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: chr1-200945956;