rs764531503

Variant names:

• chr19-49882085-C-A
• rs764531503
• NM_024682.3:c.572C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49882085-C-A
• chr19-49882085-C-T

Variant summary

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

The NM_024682.3(TBC1D17):​c.572C>A​(p.Ser191Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S191F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: TBC1D17 NM_024682.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23
• Publications: 1 publications found

Genes affected

TBC1D17 (HGNC:25699): (TBC1 domain family member 17) Predicted to enable GTPase activator activity. Involved in retrograde transport, endosome to Golgi. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904743 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
TBC1D17	NM_024682.3	c.572C>A	p.Ser191Tyr	missense_variant	Exon 6 of 17	ENST00000221543.10	NP_078958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D17	ENST00000221543.10	c.572C>A	p.Ser191Tyr	missense_variant	Exon 6 of 17	1	NM_024682.3	ENSP00000221543.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251388 AF XY: 0.00000736

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: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461826 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727214

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

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

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111990

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.79	T
PhyloP100		6.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.043	D;D
Vest4		0.65
MutPred		0.32		Loss of disorder (P = 0.0039);.;
MVP		0.69
MPC		0.76
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.57
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs764531503; hg19: chr19-50385342;