rs9672286

Variant names:

• chr15-89631558-C-T
• rs9672286
• NM_198525.3:c.3048G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-89631558-C-T
• chr15-89631558-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_198525.3(KIF7):​c.3048G>A​(p.Ser1016Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,573,864 control chromosomes in the GnomAD database, including 248,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21760 hom., cov: 34)
  • Exomes 𝑓: 0.56 (227096 hom.)
• Consequence: KIF7 NM_198525.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -1.23
• Publications: 23 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 15-89631558-C-T is Benign according to our data. Variant chr15-89631558-C-T is described in ClinVar as Benign. ClinVar VariationId is 96655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

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.3048G>A	p.Ser1016Ser	synonymous	Exon 15 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.3048G>A	p.Ser1016Ser	synonymous	Exon 15 of 19	ENSP00000377934.3	Q2M1P5
	KIF7	ENST00000696512.1		c.3171G>A	p.Ser1057Ser	synonymous	Exon 15 of 19	ENSP00000512678.1	A0A8Q3SIQ8
	KIF7	ENST00000946200.1		c.3060G>A	p.Ser1020Ser	synonymous	Exon 15 of 19	ENSP00000616259.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80806 AN: 152026 Hom.: 21740 Cov.: 34

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.514

GnomAD2 exomes AF: 0.495 AC: 94542 AN: 190910 AF XY: 0.497

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.596

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.561 AC: 798229 AN: 1421720 Hom.: 227096 Cov.: 57 AF XY: 0.559 AC XY: 393563 AN XY: 703614

African (AFR) AF: 0.475 AC: 15433 AN: 32520

American (AMR) AF: 0.407 AC: 16419 AN: 40332

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 13787 AN: 25466

East Asian (EAS) AF: 0.301 AC: 11371 AN: 37762

South Asian (SAS) AF: 0.498 AC: 40422 AN: 81228

European-Finnish (FIN) AF: 0.606 AC: 30117 AN: 49710

Middle Eastern (MID) AF: 0.456 AC: 2446 AN: 5368

European-Non Finnish (NFE) AF: 0.584 AC: 636751 AN: 1090580

Other (OTH) AF: 0.536 AC: 31483 AN: 58754

GnomAD4 genome AF: 0.532 AC: 80867 AN: 152144 Hom.: 21760 Cov.: 34 AF XY: 0.530 AC XY: 39391 AN XY: 74382

African (AFR) AF: 0.483 AC: 20045 AN: 41512

American (AMR) AF: 0.457 AC: 6990 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1730 AN: 5156

South Asian (SAS) AF: 0.479 AC: 2310 AN: 4826

European-Finnish (FIN) AF: 0.613 AC: 6500 AN: 10604

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39630 AN: 67966

Other (OTH) AF: 0.513 AC: 1084 AN: 2112

Alfa AF: 0.550 Hom.: 40389

Bravo AF: 0.516

Asia WGS AF: 0.416 AC: 1449 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	3	Acrocallosal syndrome (3)
-	-	2	not provided (2)
-	-	1	Hydrolethalus syndrome 2 (1)
-	-	1	Multiple epiphyseal dysplasia, Al-Gazali type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.81
DANN	Benign	0.92
PhyloP100		-1.2
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: rs9672286; hg19: chr15-90174789; COSMIC: COSV51542019; COSMIC: COSV51542019;