chr17-79940933-G-T

Variant names:

• chr17-79940933-G-T
• rs1299451909
• NM_019020.4:c.2230C>A

Variant summary

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

The NM_019020.4(TBC1D16):​c.2230C>A​(p.Pro744Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 6.9e-7 (0 hom.)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

Genes affected

TBC1D16 (HGNC:28356): (TBC1 domain family member 16) Enables GTPase activator activity. Involved in regulation of receptor recycling. Located in cytosol and early endosome. [provided by Alliance of Genome Resources, Apr 2022]

LINC01978 (HGNC:52806): (long intergenic non-protein coding RNA 1978)

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=0.15358105).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019020.4. 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
	TBC1D16	NM_019020.4	MANE Select	c.2230C>A	p.Pro744Thr	missense	Exon 12 of 12	NP_061893.2
	TBC1D16	NM_001271845.2		c.1144C>A	p.Pro382Thr	missense	Exon 8 of 8	NP_001258774.1	Q8TBP0-2
	TBC1D16	NM_001271844.2		c.1105C>A	p.Pro369Thr	missense	Exon 8 of 8	NP_001258773.1	Q8TBP0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D16	ENST00000310924.7	TSL:1 MANE Select	c.2230C>A	p.Pro744Thr	missense	Exon 12 of 12	ENSP00000309794.2	Q8TBP0-1
	TBC1D16	ENST00000340848.11	TSL:1	c.1144C>A	p.Pro382Thr	missense	Exon 8 of 8	ENSP00000341517.7	Q8TBP0-2
	TBC1D16	ENST00000576768.5	TSL:1	c.1105C>A	p.Pro369Thr	missense	Exon 8 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000447 AC: 1 AN: 223782 AF XY: 0.00000818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000304

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: 6.93e-7 AC: 1 AN: 1443052 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 715428

African (AFR) AF: 0.00 AC: 0 AN: 33044

American (AMR) AF: 0.0000229 AC: 1 AN: 43598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 38766

South Asian (SAS) AF: 0.00 AC: 0 AN: 84074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101548

Other (OTH) AF: 0.00 AC: 0 AN: 59390

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	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.084
Sift	Benign	0.070	T
Sift4G	Benign	0.31	T
Polyphen		0.48	P
Vest4		0.19
MutPred		0.18		Gain of phosphorylation at P744 (P = 0.0452)
MVP		0.44
MPC		0.076
ClinPred		0.18	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.46

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: rs1299451909; hg19: chr17-77914732;