chr11-43359027-C-G

Variant names:

• chr11-43359027-C-G
• rs777458379
• NM_018259.6:c.73C>G

Variant summary

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

The NM_018259.6(TTC17):​c.73C>G​(p.Leu25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,338 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L25F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TTC17 NM_018259.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.73C>G	p.Leu25Val	missense	Exon 1 of 24	NP_060729.2
	TTC17	NM_001376525.1		c.73C>G	p.Leu25Val	missense	Exon 1 of 25	NP_001363454.1	A0A994J3X0
	TTC17	NM_001376526.1		c.73C>G	p.Leu25Val	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.73C>G	p.Leu25Val	missense	Exon 1 of 24	ENSP00000039989.4	Q96AE7-1
	TTC17	ENST00000299240.10	TSL:1	c.73C>G	p.Leu25Val	missense	Exon 1 of 20	ENSP00000299240.5	Q96AE7-2
	TTC17	ENST00000867749.1		c.73C>G	p.Leu25Val	missense	Exon 1 of 25	ENSP00000537808.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439338 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715340

African (AFR) AF: 0.00 AC: 0 AN: 31664

American (AMR) AF: 0.00 AC: 0 AN: 42562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25478

East Asian (EAS) AF: 0.00 AC: 0 AN: 37122

South Asian (SAS) AF: 0.00 AC: 0 AN: 83454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102360

Other (OTH) AF: 0.00 AC: 0 AN: 59402

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.12
Sift	Uncertain	0.015	D
Sift4G	Benign	0.15	T
Polyphen		0.96	P
Vest4		0.61
MutPred		0.24		Loss of helix (P = 0.0376)
MVP		0.14
MPC		0.70
ClinPred		0.87	D
GERP RS		5.4
PromoterAI		0.0064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.25
gMVP		0.50
Mutation Taster		=84/16	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: rs777458379; hg19: chr11-43380577;