17-74356947-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080466.2(BTBD17):​c.1147G>A​(p.Ala383Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000648 in 1,234,190 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A383P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: BTBD17 NM_001080466.2 missense
• Clinical Significance: Not reported in ClinVar
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023991257).

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>A	p.Ala383Thr	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>A	p.Ala383Thr	missense	Exon 3 of 3	ENSP00000364515.3	A6NE02

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000128 AC: 2 AN: 15678 AF XY: 0.000196

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: 0.000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000648 AC: 8 AN: 1234190 Hom.: 0 Cov.: 32 AF XY: 0.00000995 AC XY: 6 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: 0.000144 AC: 8 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 Cov.: 32

ExAC AF: 0.0000406 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.14
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.62	N
REVEL	Benign	0.11
Sift	Benign	0.33	T
Sift4G	Benign	0.066	T
Polyphen		0.031	B
Vest4		0.087
MutPred		0.26		Gain of glycosylation at A383 (P = 0.0011)
MVP		0.66
ClinPred		0.029	T
GERP RS		1.4
Varity_R		0.038
gMVP		0.34
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: rs774232268; hg19: chr17-72353086;