17-79940998-G-A

Variant names:

• chr17-79940998-G-A
• rs759693304
• NM_019020.4:c.2165C>T

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.2165C>T​(p.Ala722Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,608,164 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. 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. A722E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.20
• 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=0.18615553).

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.2165C>T	p.Ala722Val	missense	Exon 12 of 12	NP_061893.2
	TBC1D16	NM_001271845.2		c.1079C>T	p.Ala360Val	missense	Exon 8 of 8	NP_001258774.1	Q8TBP0-2
	TBC1D16	NM_001271844.2		c.1040C>T	p.Ala347Val	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.2165C>T	p.Ala722Val	missense	Exon 12 of 12	ENSP00000309794.2	Q8TBP0-1
	TBC1D16	ENST00000340848.11	TSL:1	c.1079C>T	p.Ala360Val	missense	Exon 8 of 8	ENSP00000341517.7	Q8TBP0-2
	TBC1D16	ENST00000576768.5	TSL:1	c.1040C>T	p.Ala347Val	missense	Exon 8 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000211 AC: 5 AN: 237006 AF XY: 0.0000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000282

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1455940 Hom.: 0 Cov.: 32 AF XY: 0.00000967 AC XY: 7 AN XY: 723840

African (AFR) AF: 0.0000300 AC: 1 AN: 33344

American (AMR) AF: 0.0000225 AC: 1 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39450

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1110166

Other (OTH) AF: 0.0000166 AC: 1 AN: 60072

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.056
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.20
Sift	Benign	0.34	T
Sift4G	Benign	0.43	T
Polyphen		0.061	B
Vest4		0.29
MVP		0.36
MPC		0.19
ClinPred		0.34	T
GERP RS		4.8
Varity_R		0.079
gMVP		0.27
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759693304; hg19: chr17-77914797; COSMIC: COSV59988706; COSMIC: COSV59988706;