chr5-138179815-C-T

Variant names:

• chr5-138179815-C-T
• rs138569484
• NM_005733.3:c.135C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_005733.3(KIF20A):​c.135C>T​(p.Val45Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,461,868 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: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: KIF20A NM_005733.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.593
• Publications: 0 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
• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• cardiomyopathy, familial restrictive, 6

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 5-138179815-C-T is Benign according to our data. Variant chr5-138179815-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3001224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.593 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 34 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20A	NM_005733.3	MANE Select	c.135C>T	p.Val45Val	synonymous	Exon 2 of 19	NP_005724.1	O95235-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20A	ENST00000394894.8	TSL:1 MANE Select	c.135C>T	p.Val45Val	synonymous	Exon 2 of 19	ENSP00000378356.3	O95235-1
	KIF20A	ENST00000927201.1		c.135C>T	p.Val45Val	synonymous	Exon 2 of 19	ENSP00000597260.1
	KIF20A	ENST00000927194.1		c.135C>T	p.Val45Val	synonymous	Exon 2 of 19	ENSP00000597253.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251310 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.59

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

Other links and lift over

dbSNP: rs138569484; hg19: chr5-137515504;