11-13445103-A-C

Position:

• chr11-13445103-A-C

Variant summary

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

The NM_032320.7(BTBD10):​c.22T>G​(p.Tyr8Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTBD10 NM_032320.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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]

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.22T>G	p.Tyr8Asp	missense_variant	2/9	ENST00000278174.10	NP_115696.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD10	ENST00000278174.10	c.22T>G	p.Tyr8Asp	missense_variant	2/9	1	NM_032320.7	ENSP00000278174	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 30, 2024

The c.22T>G (p.Y8D) alteration is located in exon 2 (coding exon 1) of the BTBD10 gene. This alteration results from a T to G substitution at nucleotide position 22, causing the tyrosine (Y) at amino acid position 8 to be replaced by an aspartic acid (D). 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	0.15
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T;T;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.58	N;D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.26	T;D;.
Polyphen		1.0	D;.;.
Vest4		0.82
MutPred		0.21		Loss of phosphorylation at Y8 (P = 0.0047);Loss of phosphorylation at Y8 (P = 0.0047);Loss of phosphorylation at Y8 (P = 0.0047);
MVP		0.55
MPC		1.3
ClinPred		0.94	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr11-13466650;