14-37749343-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001310135.5(TTC6):c.2768G>A(p.Arg923His) variant causes a missense change. The variant allele was found at a frequency of 0.00609 in 1,491,782 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R923L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0071 (15 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (101 hom.)
• Consequence: TTC6 NM_001310135.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.80

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011599302).
• BP6: Variant 14-37749343-G-A is Benign according to our data. Variant chr14-37749343-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC6	NM_001310135.5	c.2768G>A	p.Arg923His	missense_variant	13/33	ENST00000553443.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC6	ENST00000553443.6	c.2768G>A	p.Arg923His	missense_variant	13/33	5	NM_001310135.5	P1
TTC6	ENST00000533625.5	c.*1062+10188G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00714 AC: 1086 AN: 152142 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00548 AC: 590 AN: 107608 Hom.: 9 AF XY: 0.00511 AC XY: 299 AN XY: 58560

Gnomad AFR exome AF: 0.000333

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.00728

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000187

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.00777

Gnomad OTH exome AF: 0.00533

GnomAD4 exome AF: 0.00597 AC: 8001 AN: 1339522 Hom.: 101 Cov.: 32 AF XY: 0.00604 AC XY: 3957 AN XY: 655552

Gnomad4 AFR exome AF: 0.000469

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00685

Gnomad4 EAS exome AF: 0.0000285

Gnomad4 SAS exome AF: 0.000113

Gnomad4 FIN exome AF: 0.0274

Gnomad4 NFE exome AF: 0.00622

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.00713 AC: 1086 AN: 152260 Hom.: 15 Cov.: 33 AF XY: 0.00760 AC XY: 566 AN XY: 74458

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.0114 Hom.: 11

Bravo AF: 0.00408

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00363 AC: 14

ExAC AF: 0.00211 AC: 32

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, 2023

TTC6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
Cadd	Pathogenic	32
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.33	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.49
MVP		0.82
MPC		0.26
ClinPred		0.051	T
GERP RS		5.8

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: rs184767824; hg19: chr14-38218548; COSMIC: COSV73288247;