5-40626651-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_925942.3(LOC105374737):n.219+2383T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 152,148 control chromosomes in the GnomAD database, including 603 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 0.083 (603 hom., cov: 32)
• Consequence: LOC105374737 XR_925942.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

Genes affected

LOC105374737 (HGNC:):

TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105374737	XR_925942.3	n.219+2383T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC33	ENST00000636106.1	c.222-13270A>G		intron_variant		5
TTC33	ENST00000636863.1	c.222-22615A>G		intron_variant		5
TTC33	ENST00000637375.1	c.222-57070A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12694 AN: 152030 Hom.: 603 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0835 AC: 12702 AN: 152148 Hom.: 603 Cov.: 32 AF XY: 0.0843 AC XY: 6270 AN XY: 74384

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0602 Hom.: 129

Bravo AF: 0.0783

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.95
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11955175; hg19: chr5-40626753;