9-127717702-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_144965.3(TTC16):​c.356G>A​(p.Arg119Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0044 in 1,613,942 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.0033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (29 hom.)
• Consequence: TTC16 NM_144965.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013285339).
• BS2: High Homozygotes in GnomAdExome4 at 29 gene

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>A	p.Arg119Gln	missense	Exon 4 of 14	NP_659402.1	Q8NEE8-1
	TTC16	NM_001317037.2		c.317G>A	p.Arg106Gln	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>A	p.Arg119Gln	missense	Exon 4 of 14	ENSP00000362386.3	Q8NEE8-1
	TTC16	ENST00000956085.1		c.356G>A	p.Arg119Gln	missense	Exon 4 of 13	ENSP00000626144.1
	TTC16	ENST00000862124.1		c.282+278G>A		intron	N/A	ENSP00000532183.1

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 510 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00510

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00387 AC: 973 AN: 251242 AF XY: 0.00385

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00518

Gnomad NFE exome AF: 0.00617

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00451 AC: 6592 AN: 1461662 Hom.: 29 Cov.: 32 AF XY: 0.00437 AC XY: 3174 AN XY: 727128

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.00262 AC: 117 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000893 AC: 77 AN: 86256

European-Finnish (FIN) AF: 0.00592 AC: 315 AN: 53208

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.00520 AC: 5782 AN: 1112002

Other (OTH) AF: 0.00402 AC: 243 AN: 60392

GnomAD4 genome AF: 0.00334 AC: 509 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00325 AC XY: 242 AN XY: 74460

African (AFR) AF: 0.00101 AC: 42 AN: 41564

American (AMR) AF: 0.00438 AC: 67 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

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

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00510 AC: 347 AN: 68014

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00423 Hom.: 4

Bravo AF: 0.00306

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00431 AC: 523

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00469

EpiControl AF: 0.00433

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	Premature ovarian insufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0066	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.2
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.22
Sift	Benign	0.068	T
Sift4G	Benign	0.081	T
Polyphen		1.0	D
Vest4		0.46
MVP		0.78
MPC		0.71
ClinPred		0.058	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.10
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV58852202; COSMIC: COSV58852202;