rs16926021

Variant names:

• chr10-69015573-G-A
• rs16926021
• NM_015634.4:c.1023G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015634.4(KIFBP):​c.1023G>A​(p.Gln341Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,426 control chromosomes in the GnomAD database, including 1,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (761 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (698 hom.)
• Consequence: KIFBP NM_015634.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.113
• Publications: 4 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), G2P, ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-69015573-G-A is Benign according to our data. Variant chr10-69015573-G-A is described in ClinVar as Benign. ClinVar VariationId is 158692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

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.1023G>A	p.Gln341Gln	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.1023G>A	p.Gln341Gln	synonymous	Exon 7 of 7	ENSP00000354848.4	Q96EK5
	KIFBP	ENST00000638119.2	TSL:5	c.1098G>A	p.Gln366Gln	synonymous	Exon 8 of 8	ENSP00000490026.1	A0A1B0GUA3
	KIFBP	ENST00000674660.1		c.972G>A	p.Gln324Gln	synonymous	Exon 7 of 7	ENSP00000502562.1	A0A6Q8PH45

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8310 AN: 151916 Hom.: 753 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.0336

GnomAD2 exomes AF: 0.0140 AC: 3519 AN: 250868 AF XY: 0.0106

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.00894

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000511

Gnomad OTH exome AF: 0.00836

GnomAD4 exome AF: 0.00562 AC: 8217 AN: 1461392 Hom.: 698 Cov.: 32 AF XY: 0.00487 AC XY: 3540 AN XY: 727012

African (AFR) AF: 0.195 AC: 6494 AN: 33354

American (AMR) AF: 0.00982 AC: 438 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00291 AC: 76 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5766

European-Non Finnish (NFE) AF: 0.000268 AC: 298 AN: 1111922

Other (OTH) AF: 0.0135 AC: 812 AN: 60348

GnomAD4 genome AF: 0.0549 AC: 8350 AN: 152034 Hom.: 761 Cov.: 32 AF XY: 0.0526 AC XY: 3909 AN XY: 74324

African (AFR) AF: 0.191 AC: 7896 AN: 41424

American (AMR) AF: 0.0217 AC: 332 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67980

Other (OTH) AF: 0.0333 AC: 70 AN: 2104

Alfa AF: 0.0581 Hom.: 527

Bravo AF: 0.0622

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		0.11
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: rs16926021; hg19: chr10-70775329;