NM_001114108.2:c.1471G>T

Variant names:

• chr1-54781482-C-A
• rs768367570
• NM_001114108.2:c.1471G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114108.2(TTC22):​c.1471G>T​(p.Gly491Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,323,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. G491R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TTC22 NM_001114108.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 0 publications found

Genes affected

TTC22 (HGNC:26067): (tetratricopeptide repeat domain 22) This gene encodes a protein with seven tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]

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=0.13433453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2	c.1471G>T	p.Gly491Trp	missense_variant	Exon 7 of 7	ENST00000371276.9	NP_001107580.1
TTC22	XM_011541671.3	c.1318G>T	p.Gly440Trp	missense_variant	Exon 6 of 6		XP_011539973.1
TTC22	XM_017001582.2	c.898G>T	p.Gly300Trp	missense_variant	Exon 7 of 7		XP_016857071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9	c.1471G>T	p.Gly491Trp	missense_variant	Exon 7 of 7	5	NM_001114108.2	ENSP00000360323.4
TTC22	ENST00000488771.1	n.*114G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1323424 Hom.: 0 Cov.: 32 AF XY: 0.00000154 AC XY: 1 AN XY: 650934

African (AFR) AF: 0.00 AC: 0 AN: 26340

American (AMR) AF: 0.00 AC: 0 AN: 26108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22484

East Asian (EAS) AF: 0.00 AC: 0 AN: 30308

South Asian (SAS) AF: 0.00 AC: 0 AN: 71700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1054718

Other (OTH) AF: 0.0000182 AC: 1 AN: 55048

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.21
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.090
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.013	D
Polyphen		0.89	P
Vest4		0.29
MutPred		0.25		Loss of disorder (P = 0.0119);
MVP		0.22
MPC		0.85
ClinPred		0.62	D
GERP RS		-0.93
Varity_R		0.12
gMVP		0.37
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs768367570; hg19: chr1-55247155;