16-71569894-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000353.3(TAT):​c.1085G>A​(p.Gly362Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G362V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

TAT
NM_000353.3 missense

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.92
Variant links:
Genes affected
TAT (HGNC:11573): (tyrosine aminotransferase) This nuclear gene encodes a mitochondrial protein tyrosine aminotransferase which is present in the liver and catalyzes the conversion of L-tyrosine into p-hydroxyphenylpyruvate. Mutations in this gene cause tyrosinemia (type II, Richner-Hanhart syndrome), a disorder accompanied by major skin and corneal lesions, with possible cognitive disability. A regulator gene for tyrosine aminotransferase is X-linked. [provided by RefSeq, Jul 2008]
TAT-AS1 (HGNC:51369): (TAT antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TATNM_000353.3 linkc.1085G>A p.Gly362Glu missense_variant Exon 10 of 12 ENST00000355962.5 NP_000344.1 P17735A0A140VKB7
TAT-AS1NR_103851.1 linkn.285-2126C>T intron_variant Intron 2 of 2
TAT-AS1NR_103852.1 linkn.259-2126C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TATENST00000355962.5 linkc.1085G>A p.Gly362Glu missense_variant Exon 10 of 12 1 NM_000353.3 ENSP00000348234.4 P17735

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.23
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.40
D
MetaRNN
Pathogenic
0.95
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.5
H
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-7.1
D
REVEL
Pathogenic
0.90
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.88
MutPred
0.80
Gain of solvent accessibility (P = 0.0596);
MVP
0.98
MPC
1.0
ClinPred
0.99
D
GERP RS
4.7
Varity_R
0.93
gMVP
0.95

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71603797; API