9-127717702-G-T

Variant names:

• chr9-127717702-G-T
• rs78007177
• NM_144965.3:c.356G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_144965.3(TTC16):​c.356G>T​(p.Arg119Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R119G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TTC16 NM_144965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22
• Publications: 10 publications found

Genes affected

TTC16 (HGNC:26536): (tetratricopeptide repeat domain 16)

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144965.3. 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
	TTC16	NM_144965.3	MANE Select	c.356G>T	p.Arg119Leu	missense	Exon 4 of 14	NP_659402.1	Q8NEE8-1
	TTC16	NM_001317037.2		c.317G>T	p.Arg106Leu	missense	Exon 4 of 14	NP_001303966.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC16	ENST00000373289.4	TSL:1 MANE Select	c.356G>T	p.Arg119Leu	missense	Exon 4 of 14	ENSP00000362386.3	Q8NEE8-1
	TTC16	ENST00000956085.1		c.356G>T	p.Arg119Leu	missense	Exon 4 of 13	ENSP00000626144.1
	TTC16	ENST00000862124.1		c.282+278G>T		intron	N/A	ENSP00000532183.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251242 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 6.84e-7 AC: 1 AN: 1461662 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.2
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.53		Loss of disorder (P = 0.0461)
MVP		0.81
MPC		0.75
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.41
gMVP		0.30
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs78007177; hg19: chr9-130479981;