rs1264751672

Variant names:

• chr17-74356845-C-T
• rs1264751672
• NM_001080466.2:c.1249G>A

Variant summary

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

The NM_001080466.2(BTBD17):​c.1249G>A​(p.Ala417Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 7.1e-7 (0 hom.)
• Consequence: BTBD17 NM_001080466.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

Genes affected

BTBD17 (HGNC:33758): (BTB domain containing 17) Predicted to be involved in negative regulation of viral genome replication and response to virus. Predicted to be located in plasma membrane. Predicted to colocalize with cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15337038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080466.2. 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
	BTBD17	NM_001080466.2	MANE Select	c.1249G>A	p.Ala417Thr	missense	Exon 3 of 3	NP_001073935.1	A6NE02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD17	ENST00000375366.4	TSL:1 MANE Select	c.1249G>A	p.Ala417Thr	missense	Exon 3 of 3	ENSP00000364515.3	A6NE02

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 175892 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408556 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 699018

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30160

American (AMR) AF: 0.00 AC: 0 AN: 37886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24884

East Asian (EAS) AF: 0.00 AC: 0 AN: 34728

South Asian (SAS) AF: 0.00 AC: 0 AN: 80544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092842

Other (OTH) AF: 0.00 AC: 0 AN: 58444

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.080
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.051	B
Vest4		0.15
MutPred		0.35		Gain of loop (P = 0.024)
MVP		0.83
ClinPred		0.25	T
GERP RS		4.1
Varity_R		0.092
gMVP		0.75
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: rs1264751672; hg19: chr17-72352984;