chr16-71568712-G-C

Position:

• chr16-71568712-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000353.3(TAT):​c.1223C>G​(p.Thr408Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAT NM_000353.3 missense, splice_region
• Scores: Splicing: ADA: 0.009811
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAT	NM_000353.3	c.1223C>G	p.Thr408Arg	missense_variant, splice_region_variant	11/12	ENST00000355962.5	NP_000344.1
TAT-AS1	NR_103851.1	n.284+2511G>C		intron_variant
TAT-AS1	NR_103852.1	n.258+2511G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAT	ENST00000355962.5	c.1223C>G	p.Thr408Arg	missense_variant, splice_region_variant	11/12	1	NM_000353.3	ENSP00000348234.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.090	N
REVEL	Uncertain	0.37
Sift	Benign	0.34	T
Sift4G	Benign	0.18	T
Polyphen		0.50	P
Vest4		0.58
MutPred		0.61		Gain of methylation at T408 (P = 0.1716);
MVP		0.87
MPC		0.29
ClinPred		0.50	D
GERP RS		-1.8
Varity_R		0.30
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0098
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 39
DS_DL_spliceai		0.20		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs200815080; hg19: chr16-71602615;