11-106053179-C-G

Variant names:

• chr11-106053179-C-G
• rs1282455395
• NM_198439.3:c.1510G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198439.3(KBTBD3):​c.1510G>C​(p.Ala504Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A504T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KBTBD3 NM_198439.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

Genes affected

KBTBD3 (HGNC:22934): (kelch repeat and BTB domain containing 3)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198439.3. 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
	KBTBD3	NM_198439.3	MANE Select	c.1510G>C	p.Ala504Pro	missense	Exon 4 of 4	NP_940841.1	Q8NAB2
	KBTBD3	NM_152433.4		c.1510G>C	p.Ala504Pro	missense	Exon 3 of 3	NP_689646.2
	KBTBD3	NM_001330359.2		c.1273G>C	p.Ala425Pro	missense	Exon 3 of 3	NP_001317288.1	G3V161

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD3	ENST00000531837.2	TSL:1 MANE Select	c.1510G>C	p.Ala504Pro	missense	Exon 4 of 4	ENSP00000432163.1	Q8NAB2
	KBTBD3	ENST00000526793.5	TSL:1	c.1510G>C	p.Ala504Pro	missense	Exon 3 of 3	ENSP00000436262.1	Q8NAB2
	KBTBD3	ENST00000883713.1		c.1510G>C	p.Ala504Pro	missense	Exon 4 of 4	ENSP00000553772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461314 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726940

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111738

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.22	T
PhyloP100		5.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.57
Sift	Benign	0.036	D
Sift4G	Uncertain	0.017	D
Vest4		0.87
MVP		0.93
MPC		0.68
ClinPred		0.95	D
GERP RS		6.0
gMVP		0.93
Mutation Taster		=52/48	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: rs1282455395; hg19: chr11-105923906;