Genetic Variant NM_019020.4:c.2230C>A (chr17-79940933-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019020.4(TBC1D16):c.2230C>A(p.Pro744Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,052 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TBC1D16
NM_019020.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Publications

0 publications found

Variant links:

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]

TBC1D16 links:

LINC01978 (HGNC:52806): (long intergenic non-protein coding RNA 1978)

LINC01978 links:

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ACMG classification

Classification was made for transcript

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=0.15358105).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D16	NM_019020.4	MANE Select	c.2230C>A	p.Pro744Thr	missense	Exon 12 of 12	NP_061893.2
TBC1D16	NM_001271845.2		c.1144C>A	p.Pro382Thr	missense	Exon 8 of 8	NP_001258774.1	Q8TBP0-2
TBC1D16	NM_001271844.2		c.1105C>A	p.Pro369Thr	missense	Exon 8 of 8	NP_001258773.1	Q8TBP0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D16	ENST00000310924.7	TSL:1 MANE Select	c.2230C>A	p.Pro744Thr	missense	Exon 12 of 12	ENSP00000309794.2	Q8TBP0-1
TBC1D16	ENST00000340848.11	TSL:1	c.1144C>A	p.Pro382Thr	missense	Exon 8 of 8	ENSP00000341517.7	Q8TBP0-2
TBC1D16	ENST00000576768.5	TSL:1	c.1105C>A	p.Pro369Thr	missense	Exon 8 of 8	ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000447

AC:

AN:

223782

AF XY:

0.00000818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443052

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33044

American (AMR)

AF:

0.0000229

AC:

AN:

43598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25774

East Asian (EAS)

AF:

0.00

AC:

AN:

38766

South Asian (SAS)

AF:

0.00

AC:

AN:

84074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101548

Other (OTH)

AF:

0.00

AC:

AN:

59390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

M_CAP

Benign

0.0073

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

5.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

REVEL

Benign

0.084

Sift

Benign

0.070

Sift4G

Benign

0.31

Polyphen

0.48

Vest4

0.19

MutPred

0.18

Gain of phosphorylation at P744 (P = 0.0452)

MVP

0.44

MPC

0.076

ClinPred

0.18

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.46

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over