NM_001136537.3:c.653C>G

Variant names:

• chr1-44813411-C-G
• rs370497052
• NM_001136537.3:c.653C>G

Variant summary

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

The NM_001136537.3(BTBD19):​c.653C>G​(p.Pro218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,395,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. P218L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: BTBD19 NM_001136537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 0 publications found

Genes affected

BTBD19 (HGNC:27145): (BTB domain containing 19)

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=0.1669096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136537.3. 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
	BTBD19	NM_001136537.3	MANE Select	c.653C>G	p.Pro218Arg	missense	Exon 7 of 8	NP_001130009.1	C9JJ37-1
	BTBD19	NM_001394561.1		c.914C>G	p.Pro305Arg	missense	Exon 6 of 7	NP_001381490.1
	BTBD19	NM_001394562.1		c.716C>G	p.Pro239Arg	missense	Exon 7 of 8	NP_001381491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD19	ENST00000450269.6	TSL:5 MANE Select	c.653C>G	p.Pro218Arg	missense	Exon 7 of 8	ENSP00000395461.1	C9JJ37-1
	BTBD19	ENST00000409335.6	TSL:5	c.539C>G	p.Pro180Arg	missense	Exon 5 of 6	ENSP00000386506.2	A0A0A0MSF5
	BTBD19	ENST00000718238.1		c.539C>G	p.Pro180Arg	missense	Exon 5 of 6	ENSP00000520683.1	A0A0A0MSF5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000430 AC: 6 AN: 1395656 Hom.: 0 Cov.: 32 AF XY: 0.00000726 AC XY: 5 AN XY: 688550

African (AFR) AF: 0.00 AC: 0 AN: 30792

American (AMR) AF: 0.00 AC: 0 AN: 35648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078568

Other (OTH) AF: 0.00 AC: 0 AN: 57774

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.18
Sift	Benign	0.17	T
Sift4G	Benign	0.47	T
Polyphen		0.96	D
Vest4		0.33
MutPred		0.41		Gain of MoRF binding (P = 7e-04)
MVP		0.19
ClinPred		0.66	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.59
Mutation Taster		=88/12	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: rs370497052; hg19: chr1-45279083;