Genetic Variant NM_001242672.3:c.3077G>T (chr1-2641531-C-A) – 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.3077G>T(p.Arg1026Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. R1026H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TTC34
NM_001242672.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.39

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.3077G>T	p.Arg1026Leu	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.3077G>T	p.Arg1026Leu	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4		A0A1C7CYW7
TTC34	ENST00000637179.1 link	c.1538G>T	p.Arg513Leu	missense_variant	Exon 7 of 7	5		ENSP00000490537.1		A8MYJ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1382550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682086

African (AFR)

AF:

0.00

AC:

AN:

31574

American (AMR)

AF:

0.00

AC:

AN:

35632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25112

East Asian (EAS)

AF:

0.00

AC:

AN:

35704

South Asian (SAS)

AF:

0.00

AC:

AN:

79120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078310

Other (OTH)

AF:

0.00

AC:

AN:

57838

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.82

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.082

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.30

T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

PhyloP100

-2.4

PrimateAI

Benign

0.36

REVEL

Benign

0.0080

MutPred

0.45

.;Loss of MoRF binding (P = 0.0368);

MVP

0.23

ClinPred

0.082

GERP RS

-4.8

Varity_R

0.047

gMVP

0.25

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over