NM_001114108.2:c.1020+428C>G

Variant names:

• chr1-54785555-G-C
• rs1646293576
• NM_001114108.2:c.1020+428C>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.1020+428C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 300,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: TTC22 NM_001114108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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=0.06808728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2	c.1020+428C>G		intron_variant	Intron 5 of 6	ENST00000371276.9	NP_001107580.1
TTC22	NM_017904.4	c.1110C>G	p.Phe370Leu	missense_variant	Exon 6 of 6		NP_060374.2
TTC22	XM_011541671.3	c.1020+428C>G		intron_variant	Intron 5 of 5		XP_011539973.1
TTC22	XM_017001582.2	c.447+428C>G		intron_variant	Intron 5 of 6		XP_016857071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9	c.1020+428C>G		intron_variant	Intron 5 of 6	5	NM_001114108.2	ENSP00000360323.4
TTC22	ENST00000371274.8	c.1110C>G	p.Phe370Leu	missense_variant	Exon 6 of 6	2		ENSP00000360321.4
TTC22	ENST00000448308.2	c.363+428C>G		intron_variant	Intron 3 of 3	3		ENSP00000390300.2
TTC22	ENST00000488771.1	n.2013+428C>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000333 AC: 1 AN: 300514 Hom.: 0 Cov.: 0 AF XY: 0.00000584 AC XY: 1 AN XY: 171270

African (AFR) AF: 0.00 AC: 0 AN: 8412

American (AMR) AF: 0.00 AC: 0 AN: 26894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10706

East Asian (EAS) AF: 0.00 AC: 0 AN: 9106

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158194

Other (OTH) AF: 0.00 AC: 0 AN: 13960

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
DANN	Benign	0.86
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.3
PROVEAN	Benign	1.2	N
REVEL	Benign	0.016
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.67	T
Polyphen		0.018	B
Vest4		0.20
MutPred		0.19		Gain of disorder (P = 0.0578);
MVP		0.030
ClinPred		0.099	T
GERP RS		-0.81
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1646293576; hg19: chr1-55251228;