Genetic Variant NM_018012.4:c.975C>G (chr1-245367343-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_018012.4(KIF26B):c.975C>G(p.Asn325Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N325S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF26B
NM_018012.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.899

Publications

0 publications found

Variant links:

Genes affected

KIF26B (HGNC:25484): (kinesin family member 26B) The protein encoded by this gene is an intracellular motor protein thought to transport organelles along microtubules. The encoded protein is required for kidney development. Elevated levels of this protein have been found in some breast and colorectal cancers. [provided by RefSeq, Mar 2017]

KIF26B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF26B	NM_018012.4 link	c.975C>G	p.Asn325Lys	missense_variant	Exon 3 of 15	ENST00000407071.7	NP_060482.2	Q2KJY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7 link	c.975C>G	p.Asn325Lys	missense_variant	Exon 3 of 15	1	NM_018012.4	ENSP00000385545.2		Q2KJY2-1
KIF26B	ENST00000479506.1 link	n.749C>G		non_coding_transcript_exon_variant	Exon 2 of 4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1440652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33044

American (AMR)

AF:

0.00

AC:

AN:

41372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25736

East Asian (EAS)

AF:

0.00

AC:

AN:

38608

South Asian (SAS)

AF:

0.00

AC:

AN:

82978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101890

Other (OTH)

AF:

0.00

AC:

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

0.0024

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.8

PhyloP100

0.90

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.72

MutPred

0.59

Gain of solvent accessibility (P = 0.0221);

MVP

0.59

MPC

0.35

ClinPred

0.97

GERP RS

-4.9

Varity_R

0.34

gMVP

0.56

Mutation Taster

=32/68

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over