rs1648777743

Variant names:

• chr1-92107955-C-T
• rs1648777743
• NM_001376131.1:c.616C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001376131.1(BTBD8):​c.616C>T​(p.Pro206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTBD8 NM_001376131.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38
• Publications: 0 publications found

Genes affected

BTBD8 (HGNC:21019): (BTB domain containing 8) Predicted to be involved in clathrin-dependent synaptic vesicle endocytosis; neuron projection development; and synaptic vesicle budding from endosome. Located in nucleoplasm. Colocalizes with AP-2 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3384679).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376131.1. 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
	BTBD8	NM_001376131.1	MANE Select	c.616C>T	p.Pro206Ser	missense	Exon 4 of 18	NP_001363060.1	Q5XKL5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD8	ENST00000636805.2	TSL:5 MANE Select	c.616C>T	p.Pro206Ser	missense	Exon 4 of 18	ENSP00000490161.1	Q5XKL5-3
	BTBD8	ENST00000342818.4	TSL:1	c.616C>T	p.Pro206Ser	missense	Exon 4 of 9	ENSP00000343686.3	A0A8V8N7F1
	BTBD8	ENST00000370382.7	TSL:1	n.883C>T		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727178

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111924

Other (OTH) AF: 0.00 AC: 0 AN: 60390

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	Benign	0.17
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.0091
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.24	N
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.28
Sift	Benign	0.47	T
Sift4G	Benign	0.23	T
Polyphen		0.58	P
Vest4		0.47
MutPred		0.62		Loss of ubiquitination at K202 (P = 0.0587)
MVP		0.77
MPC		0.57
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.099
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1648777743; hg19: chr1-92573512; COSMIC: COSV107434502; COSMIC: COSV107434502;