17-79942064-C-T

Variant names:

• chr17-79942064-C-T
• rs141943473
• NM_019020.4:c.2051G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_019020.4(TBC1D16):​c.2051G>A​(p.Arg684Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,610,480 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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. R684W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09559834).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.2051G>A	p.Arg684Gln	missense	Exon 11 of 12	NP_061893.2
	TBC1D16	NM_001271845.2		c.965G>A	p.Arg322Gln	missense	Exon 7 of 8	NP_001258774.1	Q8TBP0-2
	TBC1D16	NM_001271844.2		c.926G>A	p.Arg309Gln	missense	Exon 7 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.2051G>A	p.Arg684Gln	missense	Exon 11 of 12	ENSP00000309794.2	Q8TBP0-1
	TBC1D16	ENST00000340848.11	TSL:1	c.965G>A	p.Arg322Gln	missense	Exon 7 of 8	ENSP00000341517.7	Q8TBP0-2
	TBC1D16	ENST00000576768.5	TSL:1	c.926G>A	p.Arg309Gln	missense	Exon 7 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152044 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000258 AC: 63 AN: 244626 AF XY: 0.000248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00273

Gnomad EAS exome AF: 0.000220

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000228

Gnomad OTH exome AF: 0.000500

GnomAD4 exome AF: 0.000156 AC: 228 AN: 1458320 Hom.: 0 Cov.: 33 AF XY: 0.000171 AC XY: 124 AN XY: 725268

African (AFR) AF: 0.000120 AC: 4 AN: 33450

American (AMR) AF: 0.000202 AC: 9 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 77 AN: 26066

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39664

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51624

Middle Eastern (MID) AF: 0.000365 AC: 2 AN: 5482

European-Non Finnish (NFE) AF: 0.0000972 AC: 108 AN: 1111312

Other (OTH) AF: 0.000348 AC: 21 AN: 60284

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152160 Hom.: 2 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41506

American (AMR) AF: 0.000654 AC: 10 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67970

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000273

EpiControl AF: 0.000417

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	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.33	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Polyphen		0.96	D
Vest4		0.85
MVP		0.43
MPC		0.34
ClinPred		0.13	T
GERP RS		3.6
Varity_R		0.23
gMVP		0.57
Mutation Taster		=71/29	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: rs141943473; hg19: chr17-77915863;