16-71575953-C-T

Position:

chr16-71575953-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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 (★★).

Frequency

Genomes: 𝑓 0.073 ( 420 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3389 hom. )

Consequence

TAT
NM_000353.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -6.65

Variant links:

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 links:

TAT-AS1 (HGNC:51369): (TAT antisense RNA 1)

TAT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
TAT	NM_000353.3 linkuse as main transcript	c.309G>A	p.Ser103=	synonymous_variant	3/12	ENST00000355962.5	NP_000344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TAT	ENST00000355962.5 linkuse as main transcript	c.309G>A	p.Ser103=	synonymous_variant	3/12	1	NM_000353.3	ENSP00000348234	P1
TAT	ENST00000566010.1 linkuse as main transcript	n.559G>A		non_coding_transcript_exon_variant	2/2	1
TAT-AS1	ENST00000561529.1 linkuse as main transcript	n.751-2112C>T		intron_variant, non_coding_transcript_variant		5
TAT	ENST00000566094.5 linkuse as main transcript	n.405G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0727

AC:

11058

AN:

152022

Hom.:

420

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0657

AC XY:

47791

AN XY:

727226

show subpopulations

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.:

AF XY:

0.0715

AC XY:

5318

AN XY:

74394

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Tyrosinemia type II

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over