rs141356687

Variant names:

• chr11-43404016-A-C
• rs141356687
• NM_018259.6:c.1351A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-43404016-A-C
• chr11-43404016-A-G
• chr11-43404016-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018259.6(TTC17):​c.1351A>C​(p.Thr451Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T451I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC17 NM_018259.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

Genes affected

TTC17 (HGNC:25596): (tetratricopeptide repeat domain 17) Involved in actin filament polymerization and cilium organization. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16593269).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018259.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC17	NM_018259.6	MANE Select	c.1351A>C	p.Thr451Pro	missense	Exon 11 of 24	NP_060729.2
	TTC17	NM_001376525.1		c.1351A>C	p.Thr451Pro	missense	Exon 11 of 25	NP_001363454.1	A0A994J3X0
	TTC17	NM_001376526.1		c.1261A>C	p.Thr421Pro	missense	Exon 10 of 23	NP_001363455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC17	ENST00000039989.9	TSL:1 MANE Select	c.1351A>C	p.Thr451Pro	missense	Exon 11 of 24	ENSP00000039989.4	Q96AE7-1
	TTC17	ENST00000299240.10	TSL:1	c.1351A>C	p.Thr451Pro	missense	Exon 11 of 20	ENSP00000299240.5	Q96AE7-2
	TTC17	ENST00000526774.5	TSL:1	n.1261A>C		non_coding_transcript_exon	Exon 6 of 15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.25
Sift	Benign	0.086	T
Sift4G	Benign	0.12	T
Polyphen		0.95	P
Vest4		0.45
MutPred		0.12		Loss of sheet (P = 0.0457)
MVP		0.30
MPC		0.26
ClinPred		0.74	D
GERP RS		4.6
Varity_R		0.11
gMVP		0.46
Mutation Taster		=85/15	polymorphism

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: rs141356687; hg19: chr11-43425566;