8-144467053-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001369769.2(KIFC2):​c.273C>T​(p.Phe91Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000596 in 1,594,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

KIFC2
NM_001369769.2 synonymous

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.285
Variant links:
Genes affected
KIFC2 (HGNC:29530): (kinesin family member C2) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement and mitotic spindle assembly. Predicted to be located in cytoplasm. Predicted to be part of kinesin complex. Predicted to be active in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
TMEM276 (HGNC:56235): (transmembrane protein 276)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 8-144467053-C-T is Benign according to our data. Variant chr8-144467053-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3864438.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.285 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIFC2NM_001369769.2 linkc.273C>T p.Phe91Phe synonymous_variant Exon 3 of 18 ENST00000645548.2 NP_001356698.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIFC2ENST00000645548.2 linkc.273C>T p.Phe91Phe synonymous_variant Exon 3 of 18 NM_001369769.2 ENSP00000494595.1 A0A2R8YEU8

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152258
Hom.:
0
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000974
AC:
21
AN:
215572
Hom.:
0
AF XY:
0.0000672
AC XY:
8
AN XY:
119022
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000316
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000964
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000424
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000569
AC:
82
AN:
1442194
Hom.:
0
Cov.:
65
AF XY:
0.0000517
AC XY:
37
AN XY:
716034
show subpopulations
Gnomad4 AFR exome
AF:
0.000242
Gnomad4 AMR exome
AF:
0.0000235
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000407
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.0000203
Gnomad4 NFE exome
AF:
0.0000444
Gnomad4 OTH exome
AF:
0.000101
GnomAD4 genome
AF:
0.0000853
AC:
13
AN:
152376
Hom.:
0
Cov.:
35
AF XY:
0.000121
AC XY:
9
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000711
Hom.:
0
Bravo
AF:
0.0000945

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 24, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
12
DANN
Uncertain
0.98
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751667885; hg19: chr8-145692436; API