14-20293907-A-G

Position:

• chr14-20293907-A-G

Variant summary

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

The NM_138376.3(TTC5):​c.1058+1405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,030 control chromosomes in the GnomAD database, including 13,129 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 0.41 (13129 hom., cov: 32)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: TTC5 NM_138376.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

Genes affected

TTC5 (HGNC:19274): (tetratricopeptide repeat domain 5) Predicted to enable DNA binding activity and chromatin binding activity. Predicted to be involved in DNA repair. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC5	NM_138376.3	c.1058+1405T>C		intron_variant		ENST00000258821.8	NP_612385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC5	ENST00000258821.8	c.1058+1405T>C		intron_variant		1	NM_138376.3	ENSP00000258821	P1
TTC5	ENST00000383029.7	c.*603+1405T>C		intron_variant, NMD_transcript_variant		1		ENSP00000372496
TTC5	ENST00000554157.5	n.2474T>C		non_coding_transcript_exon_variant	8/9	2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62763 AN: 151896 Hom.: 13132 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.200

GnomAD4 genome AF: 0.413 AC: 62782 AN: 152014 Hom.: 13129 Cov.: 32 AF XY: 0.410 AC XY: 30442 AN XY: 74332

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.396

Alfa AF: 0.411 Hom.: 2389

Bravo AF: 0.407

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs11623837; hg19: chr14-20762066;