rs12896790

Variant names:

• chr14-37804717-T-G
• rs12896790
• NM_001310135.5:c.4067T>G

Variant summary

Our verdict is Benign. The variant received -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. 13/17 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
• Publications: 11 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TTC6	NM_001310135.5	c.4067T>G	p.Ile1356Ser	missense_variant	Exon 23 of 33	ENST00000553443.6	NP_001297064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC6	ENST00000553443.6	c.4067T>G	p.Ile1356Ser	missense_variant	Exon 23 of 33	5	NM_001310135.5	ENSP00000451131.1

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

GnomAD2 exomes AF: 0.0830 AC: 20638 AN: 248768 AF XY: 0.0898

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 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

African (AFR) AF: 0.0145 AC: 487 AN: 33476

American (AMR) AF: 0.0415 AC: 1856 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3321 AN: 26118

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39690

South Asian (SAS) AF: 0.141 AC: 12191 AN: 86214

European-Finnish (FIN) AF: 0.0974 AC: 5200 AN: 53404

Middle Eastern (MID) AF: 0.116 AC: 667 AN: 5768

European-Non Finnish (NFE) AF: 0.0944 AC: 104995 AN: 1111816

Other (OTH) AF: 0.0893 AC: 5394 AN: 60378

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

African (AFR) AF: 0.0159 AC: 661 AN: 41572

American (AMR) AF: 0.0490 AC: 750 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.132 AC: 639 AN: 4826

European-Finnish (FIN) AF: 0.0969 AC: 1029 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0976 AC: 6640 AN: 68020

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0870 Hom.: 1609

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
PhyloP100		1.3
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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