chr1-2641781-G-C

Variant names:

• chr1-2641781-G-C
• rs561866095
• NM_001242672.3:c.2827C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001242672.3(TTC34):​c.2827C>G​(p.Arg943Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,535,216 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts 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. R943W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0021 (2 hom.)
• Consequence: TTC34 NM_001242672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03015688).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC34	NM_001242672.3	c.2827C>G	p.Arg943Gly	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.2827C>G	p.Arg943Gly	missense_variant	Exon 9 of 9	5	NM_001242672.3	ENSP00000383873.4
TTC34	ENST00000637179.1	c.1288C>G	p.Arg430Gly	missense_variant	Exon 7 of 7	5		ENSP00000490537.1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152236 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00108 AC: 142 AN: 131830 AF XY: 0.000930

Gnomad AFR exome AF: 0.000159

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00171

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00188

Gnomad OTH exome AF: 0.00123

GnomAD4 exome AF: 0.00208 AC: 2870 AN: 1382862 Hom.: 2 Cov.: 36 AF XY: 0.00198 AC XY: 1353 AN XY: 682336

African (AFR) AF: 0.000348 AC: 11 AN: 31574

American (AMR) AF: 0.000954 AC: 34 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 57 AN: 25138

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35700

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79190

European-Finnish (FIN) AF: 0.000119 AC: 4 AN: 33574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00244 AC: 2634 AN: 1078514

Other (OTH) AF: 0.00219 AC: 127 AN: 57862

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152354 Hom.: 1 Cov.: 34 AF XY: 0.00117 AC XY: 87 AN XY: 74504

African (AFR) AF: 0.000313 AC: 13 AN: 41588

American (AMR) AF: 0.00163 AC: 25 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00226 AC: 154 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000683 Hom.: 0

Bravo AF: 0.00145

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00156 AC: 6

ExAC AF: 0.000293 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.78	T;.
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.030	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.9	.;M
PhyloP100		0.25
PrimateAI	Uncertain	0.63	T
REVEL	Benign	0.27
MVP		0.47
ClinPred		0.17	T
GERP RS		1.3
Varity_R		0.47
gMVP		0.78
Mutation Taster		=56/44	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: rs561866095; hg19: chr1-2573220; COSMIC: COSV105340809;