chr1-2641489-C-G

Variant names:

• chr1-2641489-C-G
• rs1027234165
• NM_001242672.3:c.3119G>C

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.3119G>C​(p.Arg1040Pro) 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 1,383,404 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. R1040H) 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: -0.648
• 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=0.17887434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.3119G>C	p.Arg1040Pro	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.3119G>C	p.Arg1040Pro	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4
TTC34	ENST00000637179.1	c.1580G>C	p.Arg527Pro	missense_variant	Exon 7 of 7	5		ENSP00000490537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383404 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 682646

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078736

Other (OTH) AF: 0.00 AC: 0 AN: 57882

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.059	.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.69	T;.
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;M
PhyloP100		-0.65
PrimateAI	Benign	0.47	T
REVEL	Benign	0.10
MutPred		0.53		.;Gain of loop (P = 0.002);
MVP		0.19
ClinPred		0.74	D
GERP RS		-0.66
Varity_R		0.39
gMVP		0.48
Mutation Taster		=83/17	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: rs1027234165; hg19: chr1-2572928;