chr14-37826179-TGGAAAATTATTTTAGGCCCAA-T

Position:

• chr14-37826179-TGGAAAATTATTTTAGGCCCAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_Moderate BP6_Moderate BS2

The NM_001310135.5(TTC6):​c.4975-7_4988del variant causes a splice acceptor, coding sequence, intron change. The variant allele was found at a frequency of 0.00517 in 1,586,596 control chromosomes in the GnomAD database, including 33 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (28 hom.)
• Consequence: TTC6 NM_001310135.5 splice_acceptor, coding_sequence, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.94

Genes affected

TTC6 (HGNC:19739): (tetratricopeptide repeat domain 6)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.02685038 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.8, offset of 28, new splice context is: ccactttaccattgccatAGata. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BP6: Variant 14-37826179-TGGAAAATTATTTTAGGCCCAA-T is Benign according to our data. Variant chr14-37826179-TGGAAAATTATTTTAGGCCCAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC6	NM_001310135.5	c.4975-7_4988del		splice_acceptor_variant, coding_sequence_variant, intron_variant	30/33	ENST00000553443.6	NP_001297064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC6	ENST00000553443.6	c.4975-7_4988del		splice_acceptor_variant, coding_sequence_variant, intron_variant	30/33	5	NM_001310135.5	ENSP00000451131	P1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152058 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00363 AC: 819 AN: 225896 Hom.: 4 AF XY: 0.00368 AC XY: 451 AN XY: 122636

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.000842

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00119

Gnomad FIN exome AF: 0.00236

Gnomad NFE exome AF: 0.00615

Gnomad OTH exome AF: 0.00484

GnomAD4 exome AF: 0.00534 AC: 7662 AN: 1434420 Hom.: 28 AF XY: 0.00521 AC XY: 3713 AN XY: 713270

Gnomad4 AFR exome AF: 0.000844

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.000733

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00136

Gnomad4 FIN exome AF: 0.00228

Gnomad4 NFE exome AF: 0.00634

Gnomad4 OTH exome AF: 0.00478

GnomAD4 genome AF: 0.00352 AC: 535 AN: 152176 Hom.: 5 Cov.: 32 AF XY: 0.00313 AC XY: 233 AN XY: 74410

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.00606

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00487 Hom.: 1

Bravo AF: 0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

TTC6: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs555569720; hg19: chr14-38295384;