Genetic Variant NM_001242672.3:c.2827C>G (chr1-2641781-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001242672.3(TTC34):c.2827C>G(p.Arg943Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,535,216 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts 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. R943W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0021 ( 2 hom. )

Consequence

TTC34
NM_001242672.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

2 publications found

Variant links:

Genes affected

TTC34 (HGNC:34297): (tetratricopeptide repeat domain 34)

TTC34 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03015688).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3 link	c.2827C>G	p.Arg943Gly	missense_variant	Exon 9 of 9	ENST00000401095.9	NP_001229601.2	A8MYJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC34	ENST00000401095.9 link	c.2827C>G	p.Arg943Gly	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4		A0A1C7CYW7
TTC34	ENST00000637179.1 link	c.1288C>G	p.Arg430Gly	missense_variant	Exon 7 of 7	5		ENSP00000490537.1		A8MYJ7

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00108

AC:

142

AN:

131830

AF XY:

0.000930

show subpopulations

Gnomad AFR exome

AF:

0.000159

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00188

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.00208

AC:

2870

AN:

1382862

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1353

AN XY:

682336

show subpopulations

African (AFR)

AF:

0.000348

AC:

AN:

31574

American (AMR)

AF:

0.000954

AC:

AN:

35658

Ashkenazi Jewish (ASJ)

AF:

0.00227

AC:

AN:

25138

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35700

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79190

European-Finnish (FIN)

AF:

0.000119

AC:

AN:

33574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00244

AC:

2634

AN:

1078514

Other (OTH)

AF:

0.00219

AC:

127

AN:

57862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

189

378

566

755

944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152354

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41588

American (AMR)

AF:

0.00163

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00226

AC:

154

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000683

Hom.:

Bravo

AF:

0.00145

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.000293

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.78

T;.

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.9

.;M

PhyloP100

0.25

PrimateAI

Uncertain

0.63

REVEL

Benign

0.27

MVP

0.47

ClinPred

0.17

GERP RS

1.3

Varity_R

0.47

gMVP

0.78

Mutation Taster

=56/44

polymorphism

(source)

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

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NM_001242672.3:c.2827C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over