1-2641403-G-C

Variant names:

• chr1-2641403-G-C
• rs764511411
• NM_001242672.3:c.3205C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001242672.3(TTC34):​c.3205C>G​(p.Arg1069Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. R1069W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TTC34 NM_001242672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2806188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.3205C>G	p.Arg1069Gly	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.3205C>G	p.Arg1069Gly	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4
TTC34	ENST00000637179.1	c.1666C>G	p.Arg556Gly	missense_variant	Exon 7 of 7	5		ENSP00000490537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375896 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 677902

African (AFR) AF: 0.00 AC: 0 AN: 31380

American (AMR) AF: 0.00 AC: 0 AN: 34910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24742

East Asian (EAS) AF: 0.00 AC: 0 AN: 35586

South Asian (SAS) AF: 0.00 AC: 0 AN: 78602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1073894

Other (OTH) AF: 0.00 AC: 0 AN: 57418

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	0.018
Eigen_PC	Benign	-0.0034
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.71	T;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	.;M
PhyloP100		0.52
PrimateAI	Benign	0.38	T
REVEL	Benign	0.22
MutPred		0.55		.;Loss of methylation at R556 (P = 0.0318);
MVP		0.33
ClinPred		0.94	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.26
gMVP		0.32
Mutation Taster		=81/19	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: rs764511411; hg19: chr1-2572842;