chr5-138179819-T-C

Position:

• chr5-138179819-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005733.3(KIF20A):​c.139T>C​(p.Ser47Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF20A NM_005733.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89

Genes affected

KIF20A (HGNC:9787): (kinesin family member 20A) Enables protein kinase binding activity. Involved in microtubule bundle formation; midbody abscission; and regulation of cytokinesis. Located in several cellular components, including cleavage furrow; intercellular bridge; and midbody. Implicated in restrictive cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

KIF20A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3731448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF20A	NM_005733.3	c.139T>C	p.Ser47Pro	missense_variant	2/19	ENST00000394894.8	NP_005724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF20A	ENST00000394894.8	c.139T>C	p.Ser47Pro	missense_variant	2/19	1	NM_005733.3	ENSP00000378356.3

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 47 of the KIF20A protein (p.Ser47Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KIF20A-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.0	.;M;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.059	T;D;D;D
Sift4G	Uncertain	0.030	D;D;D;T
Polyphen		1.0	.;D;.;.
Vest4		0.24, 0.53
MutPred		0.29		Loss of catalytic residue at S47 (P = 0.0402);Loss of catalytic residue at S47 (P = 0.0402);Loss of catalytic residue at S47 (P = 0.0402);Loss of catalytic residue at S47 (P = 0.0402);
MVP		0.89
MPC		2.5
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr5-137515508;