17-74356947-C-G

Variant names:

• chr17-74356947-C-G
• rs774232268
• NM_001080466.2:c.1147G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080466.2(BTBD17):​c.1147G>C​(p.Ala383Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A383V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BTBD17 NM_001080466.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.138
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09241846).

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.1147G>C	p.Ala383Pro	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.1147G>C	p.Ala383Pro	missense	Exon 3 of 3	ENSP00000364515.3	A6NE02

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151848 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1234190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 603200

African (AFR) AF: 0.00 AC: 0 AN: 24060

American (AMR) AF: 0.00 AC: 0 AN: 10518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17818

East Asian (EAS) AF: 0.00 AC: 0 AN: 27612

South Asian (SAS) AF: 0.00 AC: 0 AN: 55374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1013586

Other (OTH) AF: 0.00 AC: 0 AN: 50974

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151848 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74174

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67900

Other (OTH) AF: 0.00 AC: 0 AN: 2088

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	0.076
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.0	N
PhyloP100		0.14
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.60	N
REVEL	Benign	0.10
Sift	Benign	0.38	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.24		Loss of sheet (P = 0.0126)
MVP		0.43
ClinPred		0.23	T
GERP RS		1.4
Varity_R		0.057
gMVP		0.48

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: rs774232268; hg19: chr17-72353086;