Genetic Variant TTC39B:p.Asp616Gly (chr9-15172023-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152574.3(TTC39B):c.1847A>G(p.Asp616Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000089 ( 0 hom. )

Consequence

TTC39B
NM_152574.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Publications

0 publications found

Variant links:

Genes affected

TTC39B (HGNC:23704): (tetratricopeptide repeat domain 39B) Predicted to be involved in several processes, including cholesterol homeostasis; negative regulation of cholesterol storage; and regulation of cholesterol efflux. [provided by Alliance of Genome Resources, Apr 2022]

TTC39B links:

ENSG00000306734 (HGNC:):

ENSG00000306734 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057289243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152574.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC39B	NM_152574.3	MANE Select	c.1847A>G	p.Asp616Gly	missense	Exon 20 of 20	NP_689787.3	A0A8V8PNE1
TTC39B	NM_001168339.2		c.1841A>G	p.Asp614Gly	missense	Exon 20 of 20	NP_001161811.2
TTC39B	NM_001168340.2		c.1808A>G	p.Asp603Gly	missense	Exon 19 of 19	NP_001161812.2	A0A8V8NCV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC39B	ENST00000512701.7	TSL:2 MANE Select	c.1847A>G	p.Asp616Gly	missense	Exon 20 of 20	ENSP00000422496.2	A0A8V8PNE1
TTC39B	ENST00000380853.1	TSL:1	n.867A>G		non_coding_transcript_exon	Exon 7 of 7
TTC39B	ENST00000380850.9	TSL:2	c.1808A>G	p.Asp603Gly	missense	Exon 19 of 19	ENSP00000370231.5	A0A8V8NCV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

250654

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

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:

0.00000891

AC:

AN:

1459236

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.000291

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110064

Other (OTH)

AF:

0.00

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

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

0.090

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.82

M_CAP

Benign

0.011

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

REVEL

Benign

0.057

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Vest4

0.18

MVP

0.39

MPC

0.074

ClinPred

0.14

GERP RS

3.2

Varity_R

0.15

gMVP

0.52

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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