16-71566867-TAAAAAAAAA-TAAAAAAA

Variant names:

• chr16-71566867-TAA-T
• rs112731997
• NM_000353.3:c.*1275_*1276delTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000353.3(TAT):​c.*1275_*1276delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 134,452 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000030 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TAT NM_000353.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• 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 2 ACMG points.

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

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.*1275_*1276delTT		3_prime_UTR	Exon 12 of 12	NP_000344.1	P17735
	TAT-AS1	NR_103851.1		n.284+678_284+679delAA		intron	N/A
	TAT-AS1	NR_103852.1		n.258+678_258+679delAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	ENST00000355962.5	TSL:1 MANE Select	c.*1275_*1276delTT		3_prime_UTR	Exon 12 of 12	ENSP00000348234.4	P17735
	TAT	ENST00000895695.1		c.*1275_*1276delTT		3_prime_UTR	Exon 12 of 12	ENSP00000565754.1
	TAT	ENST00000895697.1		c.*1275_*1276delTT		3_prime_UTR	Exon 11 of 11	ENSP00000565756.1

Frequencies

GnomAD3 genomes AF: 0.0000298 AC: 4 AN: 134452 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000267

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000162

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000298 AC: 4 AN: 134452 Hom.: 0 Cov.: 32 AF XY: 0.0000155 AC XY: 1 AN XY: 64620

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

African (AFR) AF: 0.0000274 AC: 1 AN: 36560

American (AMR) AF: 0.00 AC: 0 AN: 13492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3184

East Asian (EAS) AF: 0.00 AC: 0 AN: 4702

South Asian (SAS) AF: 0.00 AC: 0 AN: 4316

European-Finnish (FIN) AF: 0.000267 AC: 2 AN: 7498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000162 AC: 1 AN: 61840

Other (OTH) AF: 0.00 AC: 0 AN: 1782

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
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;