5-138180092-G-C

Variant names:

• chr5-138180092-G-C
• rs10038448
• NM_005733.3:c.165+247G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005733.3(KIF20A):​c.165+247G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,120 control chromosomes in the GnomAD database, including 39,895 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39895 hom., cov: 32)
• Consequence: KIF20A NM_005733.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• familial isolated restrictive cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cardiomyopathy, familial restrictive, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005733.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20A	NM_005733.3	MANE Select	c.165+247G>C		intron	N/A	NP_005724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20A	ENST00000394894.8	TSL:1 MANE Select	c.165+247G>C		intron	N/A	ENSP00000378356.3
	KIF20A	ENST00000508792.5	TSL:2	c.165+247G>C		intron	N/A	ENSP00000420880.1
	KIF20A	ENST00000504621.1	TSL:3	c.165+247G>C		intron	N/A	ENSP00000424056.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109419 AN: 152002 Hom.: 39840 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.719

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109528 AN: 152120 Hom.: 39895 Cov.: 32 AF XY: 0.715 AC XY: 53122 AN XY: 74332

African (AFR) AF: 0.699 AC: 29003 AN: 41496

American (AMR) AF: 0.716 AC: 10945 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2379 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2155 AN: 5160

South Asian (SAS) AF: 0.789 AC: 3809 AN: 4830

European-Finnish (FIN) AF: 0.673 AC: 7112 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51893 AN: 68008

Other (OTH) AF: 0.714 AC: 1506 AN: 2108

Alfa AF: 0.729 Hom.: 4798

Bravo AF: 0.716

Asia WGS AF: 0.628 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10038448; hg19: chr5-137515781;