rs759693304

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-79940998-G-T
• chr17-79940998-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019020.4(TBC1D16):​c.2165C>A​(p.Ala722Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,455,942 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: TBC1D16 NM_019020.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18537045).

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>A	p.Ala722Glu	missense	Exon 12 of 12	NP_061893.2
	TBC1D16	NM_001271845.2		c.1079C>A	p.Ala360Glu	missense	Exon 8 of 8	NP_001258774.1	Q8TBP0-2
	TBC1D16	NM_001271844.2		c.1040C>A	p.Ala347Glu	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>A	p.Ala722Glu	missense	Exon 12 of 12	ENSP00000309794.2	Q8TBP0-1
	TBC1D16	ENST00000340848.11	TSL:1	c.1079C>A	p.Ala360Glu	missense	Exon 8 of 8	ENSP00000341517.7	Q8TBP0-2
	TBC1D16	ENST00000576768.5	TSL:1	c.1040C>A	p.Ala347Glu	missense	Exon 8 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000211 AC: 5 AN: 237006 AF XY: 0.0000232

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000206

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000941

Gnomad OTH exome AF: 0.000346

GnomAD4 exome AF: 0.00000618 AC: 9 AN: 1455942 Hom.: 0 Cov.: 32 AF XY: 0.00000553 AC XY: 4 AN XY: 723842

African (AFR) AF: 0.00 AC: 0 AN: 33344

American (AMR) AF: 0.00 AC: 0 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.00 AC: 0 AN: 85080

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

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110168

Other (OTH) AF: 0.0000832 AC: 5 AN: 60072

GnomAD4 genome Cov.: 32

Alfa AF: 0.000174 Hom.: 0

ExAC AF: 0.0000248 AC: 3

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	Benign	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.86
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.040
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		9.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.24
Sift	Benign	0.45	T
Sift4G	Benign	1.0	T
Polyphen		0.066	B
Vest4		0.38
MutPred		0.22		Gain of solvent accessibility (P = 0.0097)
MVP		0.41
MPC		0.31
ClinPred		0.35	T
GERP RS		4.8
Varity_R		0.15
gMVP		0.45
Mutation Taster		=61/39	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;