NM_001242672.3:c.3175C>G

Variant names:

• chr1-2641433-G-C
• rs895222851
• NM_001242672.3:c.3175C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242672.3(TTC34):​c.3175C>G​(p.Arg1059Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. R1059H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TTC34 NM_001242672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.25
• Publications: 0 publications found

Genes affected

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

ACMG classification

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=0.070534885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.3175C>G	p.Arg1059Gly	missense_variant	Exon 9 of 9	ENST00000401095.9	NP_001229601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC34	ENST00000401095.9	c.3175C>G	p.Arg1059Gly	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4
TTC34	ENST00000637179.1	c.1636C>G	p.Arg546Gly	missense_variant	Exon 7 of 7	5		ENSP00000490537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682292

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078378

Other (OTH) AF: 0.00 AC: 0 AN: 57838

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0010
DANN	Benign	0.63
DEOGEN2	Benign	0.0051	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.56	T;.
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	.;N
PhyloP100		-4.3
PrimateAI	Benign	0.35	T
REVEL	Benign	0.010
MutPred		0.48		.;Loss of MoRF binding (P = 0.0174);
MVP		0.18
ClinPred		0.058	T
GERP RS		-7.1
Varity_R		0.035
gMVP		0.081
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs895222851; hg19: chr1-2572872;