16-71567747-T-TAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000353.3(TAT):c.*396_*397insCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 308,026 control chromosomes in the GnomAD database, including 391 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (332 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (59 hom.)
• Consequence: TAT NM_000353.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-71567747-T-TAG is Benign according to our data. Variant chr16-71567747-T-TAG is described in ClinVar as [Likely_benign]. Clinvar id is 320396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAT	NM_000353.3	c.*396_*397insCT		3_prime_UTR_variant	12/12	ENST00000355962.5
TAT-AS1	NR_103852.1	n.258+1549_258+1550dup		intron_variant, non_coding_transcript_variant
TAT-AS1	NR_103851.1	n.284+1549_284+1550dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAT	ENST00000355962.5	c.*396_*397insCT		3_prime_UTR_variant	12/12	1	NM_000353.3	P1
TAT-AS1	ENST00000561529.1	n.284+1549_284+1550dup		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5615 AN: 152164 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.00466 AC: 726 AN: 155744 Hom.: 59 Cov.: 0 AF XY: 0.00394 AC XY: 329 AN XY: 83412

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.00882

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.000134

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00496

GnomAD4 genome AF: 0.0369 AC: 5622 AN: 152282 Hom.: 332 Cov.: 32 AF XY: 0.0364 AC XY: 2714 AN XY: 74478

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0282 Hom.: 23

Bravo AF: 0.0415

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertyrosinemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs146280073; hg19: chr16-71601650;