1-2641544-C-A

Position:

• chr1-2641544-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242672.3(TTC34):​c.3064G>T​(p.Ala1022Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,381,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TTC34 NM_001242672.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.139

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16502273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.3064G>T	p.Ala1022Ser	missense_variant	9/9	ENST00000401095.9	NP_001229601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC34	ENST00000401095.9	c.3064G>T	p.Ala1022Ser	missense_variant	9/9	5	NM_001242672.3	ENSP00000383873.4
TTC34	ENST00000637179.1	c.1525G>T	p.Ala509Ser	missense_variant	7/7	5		ENSP00000490537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000362 AC: 5 AN: 1381616 Hom.: 0 Cov.: 30 AF XY: 0.00000587 AC XY: 4 AN XY: 681536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000506

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2022

The c.1525G>T (p.A509S) alteration is located in exon 7 (coding exon 7) of the TTC34 gene. This alteration results from a G to T substitution at nucleotide position 1525, causing the alanine (A) at amino acid position 509 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.5
DANN	Benign	0.66
DEOGEN2	Benign	0.0020	.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.41	T;.
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.46	T
REVEL	Benign	0.066
MutPred		0.35		.;Gain of disorder (P = 0.057);
MVP		0.040
ClinPred		0.075	T
GERP RS		2.6
Varity_R		0.056
gMVP		0.086

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-2572983;