chr1-54800971-G-C

Variant names:

• chr1-54800971-G-C
• rs759257657
• NM_001114108.2:c.193C>G

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.193C>G​(p.Arg65Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R65S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC22 NM_001114108.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• Publications: 1 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=0.18129665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2	c.193C>G	p.Arg65Gly	missense_variant	Exon 1 of 7	ENST00000371276.9	NP_001107580.1
TTC22	NM_017904.4	c.193C>G	p.Arg65Gly	missense_variant	Exon 1 of 6		NP_060374.2
TTC22	XM_011541671.3	c.193C>G	p.Arg65Gly	missense_variant	Exon 1 of 6		XP_011539973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9	c.193C>G	p.Arg65Gly	missense_variant	Exon 1 of 7	5	NM_001114108.2	ENSP00000360323.4
TTC22	ENST00000371274.8	c.193C>G	p.Arg65Gly	missense_variant	Exon 1 of 6	2		ENSP00000360321.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L;L
PhyloP100		5.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.081
Sift	Benign	0.057	T;D
Sift4G	Benign	0.15	T;T
Polyphen		0.11	B;P
Vest4		0.18
MutPred		0.26		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.60
MPC		0.53
ClinPred		0.77	D
GERP RS		3.5
PromoterAI		0.0055	Neutral
Varity_R		0.24
gMVP		0.65
Mutation Taster		=62/38	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: rs759257657; hg19: chr1-55266644;