chr11-43359004-C-T

Variant names:

• chr11-43359004-C-T
• rs752445963
• NM_018259.6:c.50C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018259.6(TTC17):​c.50C>T​(p.Ser17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,586,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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. S17C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (1 hom.)
• Consequence: TTC17 NM_018259.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• 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]

ENSG00000254907 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.111222476).

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.50C>T	p.Ser17Phe	missense	Exon 1 of 24	NP_060729.2
	TTC17	NM_001376525.1		c.50C>T	p.Ser17Phe	missense	Exon 1 of 25	NP_001363454.1	A0A994J3X0
	TTC17	NM_001376526.1		c.50C>T	p.Ser17Phe	missense	Exon 1 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.50C>T	p.Ser17Phe	missense	Exon 1 of 24	ENSP00000039989.4	Q96AE7-1
	TTC17	ENST00000299240.10	TSL:1	c.50C>T	p.Ser17Phe	missense	Exon 1 of 20	ENSP00000299240.5	Q96AE7-2
	TTC17	ENST00000867749.1		c.50C>T	p.Ser17Phe	missense	Exon 1 of 25	ENSP00000537808.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000624 AC: 13 AN: 208216 AF XY: 0.0000605

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000425

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000181 AC: 26 AN: 1433820 Hom.: 1 Cov.: 31 AF XY: 0.0000225 AC XY: 16 AN XY: 711850

African (AFR) AF: 0.00 AC: 0 AN: 31188

American (AMR) AF: 0.000591 AC: 25 AN: 42296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 36590

South Asian (SAS) AF: 0.00 AC: 0 AN: 83348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098942

Other (OTH) AF: 0.0000169 AC: 1 AN: 59092

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74510

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000249 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.034	D
Polyphen		0.68	P
Vest4		0.38
MutPred		0.24		Loss of glycosylation at S17 (P = 0.02)
MVP		0.14
MPC		0.24
ClinPred		0.23	T
GERP RS		5.5
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.37
Mutation Taster		=80/20	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: rs752445963; hg19: chr11-43380554;