1-54783481-T-C

Variant names:

• chr1-54783481-T-C
• rs628667
• NM_001114108.2:c.1021-1004A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114108.2(TTC22):​c.1021-1004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,134 control chromosomes in the GnomAD database, including 7,051 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.

• Frequency: Genomes: 𝑓 0.30 (7051 hom., cov: 33)
• Consequence: TTC22 NM_001114108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2	c.1021-1004A>G		intron_variant	Intron 5 of 6	ENST00000371276.9	NP_001107580.1
TTC22	XM_011541671.3	c.1021-1702A>G		intron_variant	Intron 5 of 5		XP_011539973.1
TTC22	XM_017001582.2	c.448-1004A>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.1021-1004A>G		intron_variant	Intron 5 of 6	5	NM_001114108.2	ENSP00000360323.4
TTC22	ENST00000488771.1	n.2014-1004A>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45091 AN: 152016 Hom.: 7027 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45166 AN: 152134 Hom.: 7051 Cov.: 33 AF XY: 0.298 AC XY: 22139 AN XY: 74380

African (AFR) AF: 0.377 AC: 15644 AN: 41466

American (AMR) AF: 0.267 AC: 4086 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2736 AN: 5170

South Asian (SAS) AF: 0.301 AC: 1453 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2512 AN: 10598

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16833 AN: 67994

Other (OTH) AF: 0.274 AC: 578 AN: 2110

Alfa AF: 0.265 Hom.: 9724

Bravo AF: 0.302

Asia WGS AF: 0.416 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs628667; hg19: chr1-55249154;