1-44808897-C-T

Variant names:

• chr1-44808897-C-T
• rs544769415
• NM_001136537.3:c.77C>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.77C>T​(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,549,704 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: BTBD19 NM_001136537.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• 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=0.11859846).

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.77C>T	p.Pro26Leu	missense	Exon 1 of 8	NP_001130009.1	C9JJ37-1
	BTBD19	NM_001394561.1		c.77C>T	p.Pro26Leu	missense	Exon 1 of 7	NP_001381490.1
	BTBD19	NM_001394562.1		c.77C>T	p.Pro26Leu	missense	Exon 1 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.77C>T	p.Pro26Leu	missense	Exon 1 of 8	ENSP00000395461.1	C9JJ37-1
	BTBD19	ENST00000409335.6	TSL:5	c.77C>T	p.Pro26Leu	missense	Exon 1 of 6	ENSP00000386506.2	A0A0A0MSF5
	BTBD19	ENST00000718238.1		c.77C>T	p.Pro26Leu	missense	Exon 1 of 6	ENSP00000520683.1	A0A0A0MSF5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000258 AC: 4 AN: 154894 AF XY: 0.0000365

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000934

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000122 AC: 17 AN: 1397418 Hom.: 0 Cov.: 30 AF XY: 0.00000580 AC XY: 4 AN XY: 689338

African (AFR) AF: 0.0000317 AC: 1 AN: 31544

American (AMR) AF: 0.0000281 AC: 1 AN: 35536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25098

East Asian (EAS) AF: 0.00 AC: 0 AN: 35552

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.0000121 AC: 13 AN: 1077820

Other (OTH) AF: 0.0000173 AC: 1 AN: 57890

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74472

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000697 AC: 2

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	0.22
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.084
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.37
Sift	Benign	0.046	D
Sift4G	Uncertain	0.037	D
Polyphen		0.98	D
Vest4		0.43
MutPred		0.58		Loss of catalytic residue at P26 (P = 0.0179)
MVP		0.28
ClinPred		0.35	T
GERP RS		3.1
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.32
Mutation Taster		=89/11	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: rs544769415; hg19: chr1-45274569;