Genetic Variant TTC34:p.Ala906Glu (chr1-2641891-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001242672.3(TTC34):c.2717C>A(p.Ala906Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000753 in 1,328,684 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A906V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

TTC34
NM_001242672.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62

Publications

0 publications found

Variant links:

Genes affected

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

TTC34 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3 link	c.2717C>A	p.Ala906Glu	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.2717C>A	p.Ala906Glu	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4		A0A1C7CYW7
TTC34	ENST00000637179.1 link	c.1178C>A	p.Ala393Glu	missense_variant	Exon 7 of 7	5		ENSP00000490537.1		A8MYJ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.53e-7

AC:

AN:

1328684

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

648930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29994

American (AMR)

AF:

0.00

AC:

AN:

29770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21364

East Asian (EAS)

AF:

0.00

AC:

AN:

35134

South Asian (SAS)

AF:

0.00

AC:

AN:

70658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4738

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1050236

Other (OTH)

AF:

0.00

AC:

AN:

55328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.0015

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.71

T;.

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.0

.;M

PhyloP100

3.6

PrimateAI

Uncertain

0.54

REVEL

Benign

0.25

MutPred

0.52

.;Gain of solvent accessibility (P = 0.0411);

MVP

0.18

ClinPred

0.94

GERP RS

3.4

Varity_R

0.55

gMVP

0.63

Mutation Taster

=69/31

polymorphism

(source)

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

Publications

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1-2641891-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over