1-44813048-T-C

Variant names:

• chr1-44813048-T-C
• rs1330517327
• NM_001136537.3:c.467T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001136537.3(BTBD19):​c.467T>C​(p.Ile156Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: BTBD19 NM_001136537.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

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.467T>C	p.Ile156Thr	missense	Exon 5 of 8	NP_001130009.1	C9JJ37-1
	BTBD19	NM_001394561.1		c.728T>C	p.Ile243Thr	missense	Exon 4 of 7	NP_001381490.1
	BTBD19	NM_001394562.1		c.530T>C	p.Ile177Thr	missense	Exon 5 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.467T>C	p.Ile156Thr	missense	Exon 5 of 8	ENSP00000395461.1	C9JJ37-1
	BTBD19	ENST00000409335.6	TSL:5	c.353T>C	p.Ile118Thr	missense	Exon 3 of 6	ENSP00000386506.2	A0A0A0MSF5
	BTBD19	ENST00000718238.1		c.353T>C	p.Ile118Thr	missense	Exon 3 of 6	ENSP00000520683.1	A0A0A0MSF5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399228 Hom.: 0 Cov.: 32 AF XY: 0.00000725 AC XY: 5 AN XY: 690096

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078828

Other (OTH) AF: 0.00 AC: 0 AN: 58030

GnomAD4 genome Cov.: 32

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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.1	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.80		Gain of disorder (P = 0.0264)
MVP		0.25
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.88
Mutation Taster		=90/10	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: rs1330517327; hg19: chr1-45278720;