11-13421806-T-G

Variant names:

• chr11-13421806-T-G
• rs143512475
• NM_032320.7:c.134A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032320.7(BTBD10):​c.134A>C​(p.Asp45Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. D45G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTBD10 NM_032320.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1335715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032320.7. 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
	BTBD10	NM_032320.7	MANE Select	c.134A>C	p.Asp45Ala	missense	Exon 3 of 9	NP_115696.2
	BTBD10	NM_001297742.2		c.158A>C	p.Asp53Ala	missense	Exon 2 of 8	NP_001284671.1	Q9BSF8-2
	BTBD10	NM_001297741.2		c.-11A>C		5_prime_UTR	Exon 2 of 8	NP_001284670.1	B7Z503

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD10	ENST00000278174.10	TSL:1 MANE Select	c.134A>C	p.Asp45Ala	missense	Exon 3 of 9	ENSP00000278174.5	Q9BSF8-1
	BTBD10	ENST00000525864.5	TSL:1	n.122A>C		non_coding_transcript_exon	Exon 2 of 6
	BTBD10	ENST00000944229.1		c.134A>C	p.Asp45Ala	missense	Exon 3 of 10	ENSP00000614288.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461244 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.0000448 AC: 2 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111696

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.70
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.078
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.22	T
Polyphen		0.013	B
Vest4		0.29
MutPred		0.23		Gain of sheet (P = 0.0085)
MVP		0.44
MPC		0.34
ClinPred		0.59	D
GERP RS		4.0
Varity_R		0.067
gMVP		0.37
Mutation Taster		=92/8	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: rs143512475; hg19: chr11-13443353;