11-13419574-T-C

Position:

• chr11-13419574-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032320.7(BTBD10):​c.470A>G​(p.Lys157Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BTBD10 NM_032320.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

Genes affected

BTBD10 (HGNC:21445): (BTB domain containing 10) Predicted to be involved in negative regulation of neuron death; positive regulation of phosphorylation; and type B pancreatic cell proliferation. Located in fibrillar center and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BTBD10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD10	NM_032320.7	c.470A>G	p.Lys157Arg	missense_variant	4/9	ENST00000278174.10	NP_115696.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD10	ENST00000278174.10	c.470A>G	p.Lys157Arg	missense_variant	4/9	1	NM_032320.7	ENSP00000278174.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.470A>G (p.K157R) alteration is located in exon 4 (coding exon 3) of the BTBD10 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the lysine (K) at amino acid position 157 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.67	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.061	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.65
MutPred		0.31		Loss of ubiquitination at K157 (P = 0.0074);.;.;
MVP		0.58
MPC		0.86
ClinPred		0.87	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-13441121;