17-79942142-T-C

Position:

• chr17-79942142-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019020.4(TBC1D16):​c.1973A>G​(p.Glu658Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D16	NM_019020.4	c.1973A>G	p.Glu658Gly	missense_variant	11/12	ENST00000310924.7	NP_061893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D16	ENST00000310924.7	c.1973A>G	p.Glu658Gly	missense_variant	11/12	1	NM_019020.4	ENSP00000309794.2
TBC1D16	ENST00000340848.11	c.887A>G	p.Glu296Gly	missense_variant	7/8	1		ENSP00000341517.7
TBC1D16	ENST00000576768.5	c.848A>G	p.Glu283Gly	missense_variant	7/8	1		ENSP00000461522.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 12, 2024

The c.1973A>G (p.E658G) alteration is located in exon 11 (coding exon 10) of the TBC1D16 gene. This alteration results from a A to G substitution at nucleotide position 1973, causing the glutamic acid (E) at amino acid position 658 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;.
Eigen	Benign	0.052
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.85	T;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D;.;D
REVEL	Benign	0.16
Sift	Benign	0.054	T;.;T
Sift4G	Benign	0.064	T;T;T
Polyphen		0.33	B;.;.
Vest4		0.84
MVP		0.51
MPC		0.17
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.32
gMVP		0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs146172702; hg19: chr17-77915941;