NM_198525.3:c.1353C>T

Variant names:

• chr15-89648345-G-A
• rs1026714192
• NM_198525.3:c.1353C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198525.3(KIF7):​c.1353C>T​(p.Arg451Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,314,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R451R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: KIF7 NM_198525.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 0 publications found

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

KIF7 Gene-Disease associations (from GenCC):

• acrocallosal syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hydrolethalus syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hydrolethalus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• multiple epiphyseal dysplasia, Al-Gazali type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.831 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198525.3. 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
	KIF7	NM_198525.3	MANE Select	c.1353C>T	p.Arg451Arg	synonymous	Exon 5 of 19	NP_940927.2	Q2M1P5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	ENST00000394412.8	TSL:5 MANE Select	c.1353C>T	p.Arg451Arg	synonymous	Exon 5 of 19	ENSP00000377934.3	Q2M1P5
	KIF7	ENST00000696512.1		c.1476C>T	p.Arg492Arg	synonymous	Exon 5 of 19	ENSP00000512678.1	A0A8Q3SIQ8
	KIF7	ENST00000946200.1		c.1353C>T	p.Arg451Arg	synonymous	Exon 5 of 19	ENSP00000616259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1314920 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 644290

African (AFR) AF: 0.00 AC: 0 AN: 27416

American (AMR) AF: 0.00 AC: 0 AN: 28806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22980

East Asian (EAS) AF: 0.0000325 AC: 1 AN: 30770

South Asian (SAS) AF: 0.00 AC: 0 AN: 74708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3782

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040040

Other (OTH) AF: 0.00 AC: 0 AN: 54162

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1026714192; hg19: chr15-90191576;