Genetic Variant TAT:p.Arg57Gly (chr16-71576247-G-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000353.3(TAT):c.169C>G(p.Arg57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R57Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TAT
NM_000353.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

2 publications found

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 links:

TAT-AS1 (HGNC:51369): (TAT antisense RNA 1)

TAT-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.957

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	NM_000353.3	MANE Select	c.169C>G	p.Arg57Gly	missense	Exon 2 of 12	NP_000344.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAT	ENST00000355962.5	TSL:1 MANE Select	c.169C>G	p.Arg57Gly	missense	Exon 2 of 12	ENSP00000348234.4
TAT	ENST00000566010.1	TSL:1	n.265C>G		non_coding_transcript_exon	Exon 2 of 2
TAT	ENST00000566094.5	TSL:2	n.265C>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727212

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60382

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.82

MutationAssessor

Pathogenic

3.2

PhyloP100

2.9

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.8

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.91

MVP

0.98

MPC

1.0

ClinPred

1.0

GERP RS

5.0

Varity_R

0.88

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over