11-13421650-T-C

Position:

• chr11-13421650-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032320.7(BTBD10):​c.290A>G​(p.His97Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTBD10 NM_032320.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10678795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD10	NM_032320.7	c.290A>G	p.His97Arg	missense_variant	3/9	ENST00000278174.10	NP_115696.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD10	ENST00000278174.10	c.290A>G	p.His97Arg	missense_variant	3/9	1	NM_032320.7	ENSP00000278174	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459986 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726392

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 03, 2021

The c.290A>G (p.H97R) alteration is located in exon 3 (coding exon 2) of the BTBD10 gene. This alteration results from a A to G substitution at nucleotide position 290, causing the histidine (H) at amino acid position 97 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0087	T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.0073
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.13	N;N;N
REVEL	Benign	0.049
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.018	B;.;.
Vest4		0.12
MutPred		0.18		Gain of MoRF binding (P = 0.0096);.;.;
MVP		0.40
MPC		0.45
ClinPred		0.76	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-13443197;