rs12896790

Positions:

• chr14-37804717-T-G

Variant summary

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

The NM_001310135.5(TTC6):​c.4067T>G​(p.Ile1356Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 1,613,888 control chromosomes in the GnomAD database, including 7,403 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.068 (522 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6881 hom.)
• Consequence: TTC6 NM_001310135.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018881261).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC6	NM_001310135.5	c.4067T>G	p.Ile1356Ser	missense_variant	23/33	ENST00000553443.6	NP_001297064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC6	ENST00000553443.6	c.4067T>G	p.Ile1356Ser	missense_variant	23/33	5	NM_001310135.5	ENSP00000451131	P1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10360 AN: 152192 Hom.: 523 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.0702

GnomAD3 exomes AF: 0.0830 AC: 20638 AN: 248768 Hom.: 1133 AF XY: 0.0898 AC XY: 12099 AN XY: 134670

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.0981

Gnomad NFE exome AF: 0.0970

Gnomad OTH exome AF: 0.0935

GnomAD4 exome AF: 0.0918 AC: 134119 AN: 1461578 Hom.: 6881 Cov.: 31 AF XY: 0.0936 AC XY: 68060 AN XY: 727082

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0974

Gnomad4 NFE exome AF: 0.0944

Gnomad4 OTH exome AF: 0.0893

GnomAD4 genome AF: 0.0680 AC: 10359 AN: 152310 Hom.: 522 Cov.: 32 AF XY: 0.0680 AC XY: 5067 AN XY: 74468

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0490

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0929 Hom.: 1222

Bravo AF: 0.0612

ESP6500AA AF: 0.0204 AC: 90

ESP6500EA AF: 0.102 AC: 877

ExAC AF: 0.0839 AC: 10190

Asia WGS AF: 0.0460 AC: 160 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.030	T;T;T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.70	T;.;T;T
MetaRNN	Benign	0.0019	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.16	T;D;D;T
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.31	B;B;B;.
Vest4		0.13
MPC		0.15
ClinPred		0.0075	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083

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: rs12896790; hg19: chr14-38273922; COSMIC: COSV99032049; COSMIC: COSV99032049;