NM_032320.7:c.713G>A

Variant names:

• chr11-13413625-C-T
• rs368074216
• NM_032320.7:c.713G>A

Variant summary

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

The NM_032320.7(BTBD10):​c.713G>A​(p.Arg238His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,610,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R238C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: BTBD10 NM_032320.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84
• Publications: 3 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.

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.713G>A	p.Arg238His	missense	Exon 6 of 9	NP_115696.2
	BTBD10	NM_001297742.2		c.737G>A	p.Arg246His	missense	Exon 5 of 8	NP_001284671.1	Q9BSF8-2
	BTBD10	NM_001297741.2		c.569G>A	p.Arg190His	missense	Exon 5 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.713G>A	p.Arg238His	missense	Exon 6 of 9	ENSP00000278174.5	Q9BSF8-1
	BTBD10	ENST00000525864.5	TSL:1	n.701G>A		non_coding_transcript_exon	Exon 5 of 6
	BTBD10	ENST00000944229.1		c.713G>A	p.Arg238His	missense	Exon 6 of 10	ENSP00000614288.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000562 AC: 14 AN: 249064 AF XY: 0.0000817

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000589

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000405 AC: 59 AN: 1458000 Hom.: 0 Cov.: 30 AF XY: 0.0000551 AC XY: 40 AN XY: 725388

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.0000451 AC: 2 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26036

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39472

South Asian (SAS) AF: 0.000467 AC: 40 AN: 85652

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1110052

Other (OTH) AF: 0.0000166 AC: 1 AN: 60248

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	0.30	N
PhyloP100		7.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.58
Sift	Benign	0.031	D
Sift4G	Benign	0.10	T
Polyphen		0.49	P
Vest4		0.60
MutPred		0.55		Gain of catalytic residue at C239 (P = 0.0591)
MVP		0.85
MPC		1.5
ClinPred		0.45	T
GERP RS		5.3
Varity_R		0.32
gMVP		0.68
Mutation Taster		=8/92	disease causing

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: rs368074216; hg19: chr11-13435172; COSMIC: COSV53398498;