16-71575953-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000353.3(TAT):c.309G>A(p.Ser103=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,613,964 control chromosomes in the GnomAD database, including 3,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S103S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.073 (420 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3389 hom.)
• Consequence: TAT NM_000353.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.65

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-71575953-C-T is Benign according to our data. Variant chr16-71575953-C-T is described in ClinVar as [Benign]. Clinvar id is 255935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-71575953-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-6.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAT	NM_000353.3	c.309G>A	p.Ser103=	synonymous_variant	3/12	ENST00000355962.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAT	ENST00000355962.5	c.309G>A	p.Ser103=	synonymous_variant	3/12	1	NM_000353.3	P1
TAT	ENST00000566010.1	n.559G>A		non_coding_transcript_exon_variant	2/2	1
TAT-AS1	ENST00000561529.1	n.751-2112C>T		intron_variant, non_coding_transcript_variant		5
TAT	ENST00000566094.5	n.405G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11058 AN: 152022 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0909

GnomAD3 exomes AF: 0.0637 AC: 16021 AN: 251480 Hom.: 577 AF XY: 0.0653 AC XY: 8874 AN XY: 135916

Gnomad AFR exome AF: 0.0992

Gnomad AMR exome AF: 0.0599

Gnomad ASJ exome AF: 0.0610

Gnomad EAS exome AF: 0.00332

Gnomad SAS exome AF: 0.0842

Gnomad FIN exome AF: 0.0540

Gnomad NFE exome AF: 0.0664

Gnomad OTH exome AF: 0.0596

GnomAD4 exome AF: 0.0653 AC: 95489 AN: 1461824 Hom.: 3389 Cov.: 31 AF XY: 0.0657 AC XY: 47791 AN XY: 727226

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.0560

Gnomad4 EAS exome AF: 0.00866

Gnomad4 SAS exome AF: 0.0844

Gnomad4 FIN exome AF: 0.0531

Gnomad4 NFE exome AF: 0.0657

Gnomad4 OTH exome AF: 0.0644

GnomAD4 genome AF: 0.0727 AC: 11064 AN: 152140 Hom.: 420 Cov.: 32 AF XY: 0.0715 AC XY: 5318 AN XY: 74394

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.0718 Hom.: 212

Bravo AF: 0.0751

Asia WGS AF: 0.0500 AC: 173 AN: 3478

EpiCase AF: 0.0686

EpiControl AF: 0.0696

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tyrosinemia type II Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.58
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs78302875; hg19: chr16-71609856; COSMIC: COSV63532487;