14-37826179-TGGAAAATTATTTTAGGCCCAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_ModerateBP6_ModerateBS2

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.94
Variant links:
Genes affected
TTC6 (HGNC:19739): (tetratricopeptide repeat domain 6)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
TTC6NM_001310135.5 linkuse as main transcriptc.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
TTC6ENST00000553443.6 linkuse as main transcriptc.4975-7_4988del splice_acceptor_variant, coding_sequence_variant, intron_variant 30/335 NM_001310135.5 ENSP00000451131 P1

Frequencies

GnomAD3 genomes
AF:
0.00352
AC:
535
AN:
152058
Hom.:
5
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023TTC6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs555569720; hg19: chr14-38295384; API