16-71566867-TAAAAAAAAA-TAAAAAAAA

Variant names:

• chr16-71566867-TA-T
• rs112731997
• NM_000353.3:c.*1276delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000353.3(TAT):​c.*1276delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TAT NM_000353.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.565
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	NM_000353.3	MANE Select	c.*1276delT		3_prime_UTR	Exon 12 of 12	NP_000344.1	P17735
	TAT-AS1	NR_103851.1		n.284+679delA		intron	N/A
	TAT-AS1	NR_103852.1		n.258+679delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	ENST00000355962.5	TSL:1 MANE Select	c.*1276delT		3_prime_UTR	Exon 12 of 12	ENSP00000348234.4	P17735
	TAT	ENST00000895695.1		c.*1276delT		3_prime_UTR	Exon 12 of 12	ENSP00000565754.1
	TAT	ENST00000895697.1		c.*1276delT		3_prime_UTR	Exon 11 of 11	ENSP00000565756.1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 200 AN: 134216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00134

Gnomad ASJ AF: 0.00157

Gnomad EAS AF: 0.000426

Gnomad SAS AF: 0.000232

Gnomad FIN AF: 0.00683

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00112

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00149 AC: 200 AN: 134238 Hom.: 0 Cov.: 32 AF XY: 0.00170 AC XY: 110 AN XY: 64520

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00120 AC: 44 AN: 36616

American (AMR) AF: 0.00133 AC: 18 AN: 13484

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 5 AN: 3180

East Asian (EAS) AF: 0.000428 AC: 2 AN: 4678

South Asian (SAS) AF: 0.000233 AC: 1 AN: 4290

European-Finnish (FIN) AF: 0.00683 AC: 51 AN: 7472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.00125 AC: 77 AN: 61672

Other (OTH) AF: 0.00112 AC: 2 AN: 1792

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hypertyrosinemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112731997; hg19: chr16-71600770;