rs41279644

Variant names:

• chr10-69016311-T-C
• rs41279644
• NM_015634.4:c.1761T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015634.4(KIFBP):​c.1761T>C​(p.Pro587Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,608,528 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (38 hom.)
• Consequence: KIFBP NM_015634.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.437
• Publications: 1 publications found

Genes affected

KIFBP (HGNC:23419): (kinesin family binding protein) This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

KIFBP Gene-Disease associations (from GenCC):

• Goldberg-Shprintzen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-69016311-T-C is Benign according to our data. Variant chr10-69016311-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.437 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0051 (777/152348) while in subpopulation NFE AF = 0.00611 (416/68032). AF 95% confidence interval is 0.00563. There are 7 homozygotes in GnomAd4. There are 448 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015634.4. 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
	KIFBP	NM_015634.4	MANE Select	c.1761T>C	p.Pro587Pro	synonymous	Exon 7 of 7	NP_056449.1	Q96EK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFBP	ENST00000361983.7	TSL:1 MANE Select	c.1761T>C	p.Pro587Pro	synonymous	Exon 7 of 7	ENSP00000354848.4	Q96EK5
	KIFBP	ENST00000638119.2	TSL:5	c.1836T>C	p.Pro612Pro	synonymous	Exon 8 of 8	ENSP00000490026.1	A0A1B0GUA3
	KIFBP	ENST00000674660.1		c.1710T>C	p.Pro570Pro	synonymous	Exon 7 of 7	ENSP00000502562.1	A0A6Q8PH45

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 778 AN: 152230 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00585 AC: 1444 AN: 246692 AF XY: 0.00585

Gnomad AFR exome AF: 0.000681

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.000309

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0261

Gnomad NFE exome AF: 0.00649

Gnomad OTH exome AF: 0.00404

GnomAD4 exome AF: 0.00613 AC: 8932 AN: 1456180 Hom.: 38 Cov.: 32 AF XY: 0.00595 AC XY: 4308 AN XY: 724328

African (AFR) AF: 0.000908 AC: 30 AN: 33036

American (AMR) AF: 0.00181 AC: 78 AN: 43044

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 8 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00227 AC: 195 AN: 85776

European-Finnish (FIN) AF: 0.0237 AC: 1265 AN: 53328

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5730

European-Non Finnish (NFE) AF: 0.00641 AC: 7117 AN: 1109726

Other (OTH) AF: 0.00394 AC: 237 AN: 60082

GnomAD4 genome AF: 0.00510 AC: 777 AN: 152348 Hom.: 7 Cov.: 32 AF XY: 0.00601 AC XY: 448 AN XY: 74508

African (AFR) AF: 0.000890 AC: 37 AN: 41592

American (AMR) AF: 0.00287 AC: 44 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00611 AC: 416 AN: 68032

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00540 Hom.: 5

Bravo AF: 0.00327

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00447

EpiControl AF: 0.00439

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Goldberg-Shprintzen syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism

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: rs41279644; hg19: chr10-70776067;