17-74356887-C-T

Variant names:

• chr17-74356887-C-T
• NM_001080466.2:c.1207G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080466.2(BTBD17):​c.1207G>A​(p.Asp403Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,331,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: BTBD17 NM_001080466.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD17	NM_001080466.2	c.1207G>A	p.Asp403Asn	missense_variant	Exon 3 of 3	ENST00000375366.4	NP_001073935.1
BTBD17	XM_011524791.3	c.1210G>A	p.Asp404Asn	missense_variant	Exon 5 of 5		XP_011523093.1
BTBD17	XM_017024622.2	c.1210G>A	p.Asp404Asn	missense_variant	Exon 5 of 5		XP_016880111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD17	ENST00000375366.4	c.1207G>A	p.Asp403Asn	missense_variant	Exon 3 of 3	1	NM_001080466.2	ENSP00000364515.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000225 AC: 3 AN: 1331850 Hom.: 0 Cov.: 32 AF XY: 0.00000304 AC XY: 2 AN XY: 657550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000286

Gnomad4 NFE exome AF: 0.00000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1207G>A (p.D403N) alteration is located in exon 3 (coding exon 3) of the BTBD17 gene. This alteration results from a G to A substitution at nucleotide position 1207, causing the aspartic acid (D) at amino acid position 403 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0083	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.56	N
REVEL	Uncertain	0.47
Sift	Benign	0.12	T
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.71		Gain of MoRF binding (P = 0.0462);
MVP		0.92
ClinPred		0.94	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.60

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-72353026;