6-33398086-G-T

Variant names:

• chr6-33398086-G-T
• NM_002263.4:c.70G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002263.4(KIFC1):​c.70G>T​(p.Ala24Ser) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIFC1 NM_002263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.842

Genes affected

KIFC1 (HGNC:6389): (kinesin family member C1) Predicted to enable microtubule binding activity and minus-end-directed microtubule motor activity. Involved in mitotic metaphase plate congression and mitotic spindle assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0533776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.70G>T	p.Ala24Ser	missense_variant	Exon 2 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.70G>T	p.Ala24Ser	missense_variant	Exon 2 of 12		XP_011512887.1
KIFC1	XM_011514587.3	c.70G>T	p.Ala24Ser	missense_variant	Exon 2 of 10		XP_011512889.1
KIFC1	XM_017010837.2	c.-54G>T		5_prime_UTR_variant	Exon 2 of 11		XP_016866326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC1	ENST00000428849.7	c.70G>T	p.Ala24Ser	missense_variant	Exon 2 of 11	1	NM_002263.4	ENSP00000393963.2
KIFC1	ENST00000450504.1	c.70G>T	p.Ala24Ser	missense_variant	Exon 2 of 7	3		ENSP00000409539.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70G>T (p.A24S) alteration is located in exon 2 (coding exon 2) of the KIFC1 gene. This alteration results from a G to T substitution at nucleotide position 70, causing the alanine (A) at amino acid position 24 to be replaced by a serine (S). 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	0.075
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.037
Sift	Benign	0.46	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0030	B;.
Vest4		0.20
MutPred		0.18		Gain of phosphorylation at A24 (P = 0.0169);Gain of phosphorylation at A24 (P = 0.0169);
MVP		0.69
MPC		0.36
ClinPred		0.055	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.019
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr6-33365863;