rs762358705

Variant names:

• chr1-2641439-C-G
• rs762358705
• NM_001242672.3:c.3169G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-2641439-C-G
• chr1-2641439-C-T

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.3169G>C​(p.Asp1057His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,980 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. D1057N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TTC34 NM_001242672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• 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=0.084114194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.3169G>C	p.Asp1057His	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.3169G>C	p.Asp1057His	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4
TTC34	ENST00000637179.1	c.1630G>C	p.Asp544His	missense_variant	Exon 7 of 7	5		ENSP00000490537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1382980 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682386

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25114

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33806

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5670

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078448

Other (OTH) AF: 0.00 AC: 0 AN: 57844

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.20
DANN	Benign	0.77
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.57	T;.
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N
PhyloP100		-1.4
PrimateAI	Benign	0.45	T
REVEL	Benign	0.013
MutPred		0.31		.;Loss of solvent accessibility (P = 0.0217);
MVP		0.14
ClinPred		0.033	T
GERP RS		-0.69
Varity_R		0.052
gMVP		0.22
Mutation Taster		=98/2	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: rs762358705; hg19: chr1-2572878;