chr17-79942104-C-T

Variant names:

• chr17-79942104-C-T
• rs770778543
• NM_019020.4:c.2011G>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.2011G>A​(p.Gly671Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,612,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 1 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=0.23604283).

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.2011G>A	p.Gly671Arg	missense	Exon 11 of 12	NP_061893.2
	TBC1D16	NM_001271845.2		c.925G>A	p.Gly309Arg	missense	Exon 7 of 8	NP_001258774.1	Q8TBP0-2
	TBC1D16	NM_001271844.2		c.886G>A	p.Gly296Arg	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.2011G>A	p.Gly671Arg	missense	Exon 11 of 12	ENSP00000309794.2	Q8TBP0-1
	TBC1D16	ENST00000340848.11	TSL:1	c.925G>A	p.Gly309Arg	missense	Exon 7 of 8	ENSP00000341517.7	Q8TBP0-2
	TBC1D16	ENST00000576768.5	TSL:1	c.886G>A	p.Gly296Arg	missense	Exon 7 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000686 AC: 17 AN: 247928 AF XY: 0.0000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00100

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.0000459 AC: 67 AN: 1460064 Hom.: 0 Cov.: 33 AF XY: 0.0000427 AC XY: 31 AN XY: 726214

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00123 AC: 32 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85978

European-Finnish (FIN) AF: 0.0000382 AC: 2 AN: 52334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111718

Other (OTH) AF: 0.0000828 AC: 5 AN: 60350

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000495 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	Pathogenic	0.94
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.092	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.072
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.011	D
Polyphen		0.93	P
Vest4		0.77
MutPred		0.47		Gain of solvent accessibility (P = 0.1319)
MVP		0.58
MPC		0.29
ClinPred		0.28	T
GERP RS		4.5
Varity_R		0.21
gMVP		0.59
Mutation Taster		=65/35	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: rs770778543; hg19: chr17-77915903;