chr17-79942080-C-G

Variant names:

• chr17-79942080-C-G
• rs1278973760
• NM_019020.4:c.2035G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019020.4(TBC1D16):​c.2035G>C​(p.Gly679Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.21
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

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.2035G>C	p.Gly679Arg	missense	Exon 11 of 12	NP_061893.2
	TBC1D16	NM_001271845.2		c.949G>C	p.Gly317Arg	missense	Exon 7 of 8	NP_001258774.1	Q8TBP0-2
	TBC1D16	NM_001271844.2		c.910G>C	p.Gly304Arg	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.2035G>C	p.Gly679Arg	missense	Exon 11 of 12	ENSP00000309794.2	Q8TBP0-1
	TBC1D16	ENST00000340848.11	TSL:1	c.949G>C	p.Gly317Arg	missense	Exon 7 of 8	ENSP00000341517.7	Q8TBP0-2
	TBC1D16	ENST00000576768.5	TSL:1	c.910G>C	p.Gly304Arg	missense	Exon 7 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Benign	0.39	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.61		Gain of MoRF binding (P = 0.0353)
MVP		0.75
MPC		0.35
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.85
gMVP		0.91

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: rs1278973760; hg19: chr17-77915879;