9-127720334-A-T

Variant names:

• chr9-127720334-A-T
• rs199988634
• NM_144965.3:c.596A>T

Variant summary

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

The NM_144965.3(TTC16):​c.596A>T​(p.Gln199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,613,322 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. Q199R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (3 hom.)
• Consequence: TTC16 NM_144965.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.335
• Publications: 3 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=0.016613662).
• BS2: High Homozygotes in GnomAdExome4 at 3 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.596A>T	p.Gln199Leu	missense	Exon 6 of 14	NP_659402.1	Q8NEE8-1
	TTC16	NM_001317037.2		c.557A>T	p.Gln186Leu	missense	Exon 6 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.596A>T	p.Gln199Leu	missense	Exon 6 of 14	ENSP00000362386.3	Q8NEE8-1
	TTC16	ENST00000956085.1		c.596A>T	p.Gln199Leu	missense	Exon 6 of 13	ENSP00000626144.1
	TTC16	ENST00000862124.1		c.452A>T	p.Gln151Leu	missense	Exon 5 of 13	ENSP00000532183.1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000851

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000306 AC: 77 AN: 251224 AF XY: 0.000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000344 AC: 503 AN: 1461128 Hom.: 3 Cov.: 35 AF XY: 0.000378 AC XY: 275 AN XY: 726864

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00107 AC: 92 AN: 86258

European-Finnish (FIN) AF: 0.000549 AC: 29 AN: 52794

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000315 AC: 350 AN: 1111922

Other (OTH) AF: 0.000348 AC: 21 AN: 60376

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74422

African (AFR) AF: 0.0000481 AC: 2 AN: 41556

American (AMR) AF: 0.000392 AC: 6 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.000851 AC: 9 AN: 10576

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

European-Non Finnish (NFE) AF: 0.000383 AC: 26 AN: 67968

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000223 Hom.: 1

Bravo AF: 0.000317

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000362 AC: 44

Asia WGS AF: 0.000577 AC: 3 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.1
DANN	Benign	0.77
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.34
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.046
Sift	Benign	0.34	T
Sift4G	Benign	0.20	T
Polyphen		0.0030	B
Vest4		0.27
MVP		0.47
MPC		0.15
ClinPred		0.027	T
GERP RS		-1.8
Varity_R		0.069
gMVP		0.12
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: rs199988634; hg19: chr9-130482613;