rs756894540

Variant names:

• chr17-79940972-C-G
• rs756894540
• NM_019020.4:c.2191G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-79940972-C-G
• chr17-79940972-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019020.4(TBC1D16):​c.2191G>C​(p.Gly731Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. G731S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18394032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D16	NM_019020.4	c.2191G>C	p.Gly731Arg	missense_variant	Exon 12 of 12	ENST00000310924.7	NP_061893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D16	ENST00000310924.7	c.2191G>C	p.Gly731Arg	missense_variant	Exon 12 of 12	1	NM_019020.4	ENSP00000309794.2
TBC1D16	ENST00000340848.11	c.1105G>C	p.Gly369Arg	missense_variant	Exon 8 of 8	1		ENSP00000341517.7
TBC1D16	ENST00000576768.5	c.1066G>C	p.Gly356Arg	missense_variant	Exon 8 of 8	1		ENSP00000461522.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.89	N;.;N
REVEL	Benign	0.097
Sift	Benign	0.083	T;.;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.34	B;.;.
Vest4		0.17
MutPred		0.20		Gain of solvent accessibility (P = 0.0097);.;.;
MVP		0.53
MPC		0.12
ClinPred		0.90	D
GERP RS		4.8
Varity_R		0.099
gMVP		0.35

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: rs756894540; hg19: chr17-77914771;