chr14-37826179-TGGAAAATTATTTTAGGCCCAA-T

Position:

• chr14-37826179-TGGAAAATTATTTTAGGCCCAA-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001310135.5(TTC6):​c.4975-7_4988delATTTTAGGCCCAAGGAAAATT​(p.Ala1659fs) variant causes a frameshift, splice acceptor, splice region, 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 (★). Variant results in nonsense mediated mRNA decay.

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

Genes affected

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

TTC6 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• 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_4988delATTTTAGGCCCAAGGAAAATT	p.Ala1659fs	frameshift_variant, splice_acceptor_variant, splice_region_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_4988delATTTTAGGCCCAAGGAAAATT	p.Ala1659fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	30/33	5	NM_001310135.5	ENSP00000451131.1

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

Sep 01, 2024

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;