1-44810323-C-T

Variant names:

• chr1-44810323-C-T
• rs1274933383
• NM_001136537.3:c.197C>T

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.197C>T​(p.Pro66Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: BTBD19 NM_001136537.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• 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=0.11489391).

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.197C>T	p.Pro66Leu	missense	Exon 2 of 8	NP_001130009.1	C9JJ37-1
	BTBD19	NM_001394561.1		c.197C>T	p.Pro66Leu	missense	Exon 2 of 7	NP_001381490.1
	BTBD19	NM_001394562.1		c.197C>T	p.Pro66Leu	missense	Exon 2 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.197C>T	p.Pro66Leu	missense	Exon 2 of 8	ENSP00000395461.1	C9JJ37-1
	BTBD19	ENST00000409335.6	TSL:5	c.197C>T	p.Pro66Leu	missense	Exon 2 of 6	ENSP00000386506.2	A0A0A0MSF5
	BTBD19	ENST00000718238.1		c.197C>T	p.Pro66Leu	missense	Exon 2 of 6	ENSP00000520683.1	A0A0A0MSF5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.082
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.69
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.22	T
Sift4G	Uncertain	0.030	D
Polyphen		0.0070	B
Vest4		0.21
MutPred		0.48		Gain of catalytic residue at P66 (P = 0.0099)
MVP		0.14
ClinPred		0.12	T
GERP RS		4.1
Varity_R		0.076
gMVP		0.20
Mutation Taster		=94/6	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: rs1274933383; hg19: chr1-45275995;