rs761340826

Variant names:

• chrX-70290433-C-T
• rs761340826
• NM_012310.5:c.-21-5C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_012310.5(KIF4A):​c.-21-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000693 in 1,197,552 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.000067 (0 hom. 24 hem.)
• Consequence: KIF4A NM_012310.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006030
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: -3.32
• Publications: 0 publications found

Genes affected

KIF4A (HGNC:13339): (kinesin family member 4A) This gene encodes a member of the kinesin 4 subfamily of kinesin related proteins. The encoded protein is an ATP dependent microtubule-based motor protein that is involved in the intracellular transport of membranous organelles. This protein also associates with condensed chromosome arms and may be involved in maintaining chromosome integrity during mitosis. This protein may also be involved in the organization of the central spindle prior to cytokinesis. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, Mar 2010]

PDZD11 (HGNC:28034): (PDZ domain containing 11) Enables protein C-terminus binding activity. Involved in pore complex assembly. Located in basolateral plasma membrane and cytosol. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-70290433-C-T is Benign according to our data. Variant chrX-70290433-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1205956.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 4 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012310.5. 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
	KIF4A	NM_012310.5	MANE Select	c.-21-5C>T		splice_region intron	N/A	NP_036442.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF4A	ENST00000374403.4	TSL:1 MANE Select	c.-21-5C>T		splice_region intron	N/A	ENSP00000363524.3	O95239-1
	KIF4A	ENST00000859345.1		c.-26C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 30	ENSP00000529404.1
	KIF4A	ENST00000924311.1		c.-26C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 31	ENSP00000594370.1

Frequencies

GnomAD3 genomes AF: 0.0000898 AC: 10 AN: 111405 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000566

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000123 AC: 21 AN: 170665 AF XY: 0.0000884

Gnomad AFR exome AF: 0.0000775

Gnomad AMR exome AF: 0.000390

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000241

GnomAD4 exome AF: 0.0000672 AC: 73 AN: 1086147 Hom.: 0 Cov.: 29 AF XY: 0.0000677 AC XY: 24 AN XY: 354333

African (AFR) AF: 0.0000383 AC: 1 AN: 26098

American (AMR) AF: 0.000381 AC: 13 AN: 34103

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18798

East Asian (EAS) AF: 0.00 AC: 0 AN: 30064

South Asian (SAS) AF: 0.00 AC: 0 AN: 52415

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40203

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3122

European-Non Finnish (NFE) AF: 0.0000610 AC: 51 AN: 835837

Other (OTH) AF: 0.000176 AC: 8 AN: 45507

GnomAD4 genome AF: 0.0000898 AC: 10 AN: 111405 Hom.: 0 Cov.: 22 AF XY: 0.000119 AC XY: 4 AN XY: 33589

African (AFR) AF: 0.00 AC: 0 AN: 30563

American (AMR) AF: 0.000661 AC: 7 AN: 10598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3540

South Asian (SAS) AF: 0.00 AC: 0 AN: 2617

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.0000566 AC: 3 AN: 53017

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.90
PhyloP100		-3.3
PromoterAI		-0.051	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.0020
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: rs761340826; hg19: chrX-69510283;