16-71575953-C-T

Variant names:

• chr16-71575953-C-T
• rs78302875
• NM_000353.3:c.309G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000353.3(TAT):​c.309G>A​(p.Ser103Ser) 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:5
• Conservation: PhyloP100: -6.65
• Publications: 10 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: Benign. The variant received -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 VariationId is 255935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
TAT	NM_000353.3	c.309G>A	p.Ser103Ser	synonymous_variant	Exon 3 of 12	ENST00000355962.5	NP_000344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAT	ENST00000355962.5	c.309G>A	p.Ser103Ser	synonymous_variant	Exon 3 of 12	1	NM_000353.3	ENSP00000348234.4
TAT	ENST00000566010.1	n.559G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
TAT	ENST00000566094.5	n.405G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
TAT-AS1	ENST00000561529.1	n.751-2112C>T		intron_variant	Intron 3 of 3	5

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

GnomAD2 exomes AF: 0.0637 AC: 16021 AN: 251480 AF XY: 0.0653

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 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

African (AFR) AF: 0.102 AC: 3422 AN: 33480

American (AMR) AF: 0.0618 AC: 2762 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 1464 AN: 26136

East Asian (EAS) AF: 0.00866 AC: 344 AN: 39700

South Asian (SAS) AF: 0.0844 AC: 7278 AN: 86258

European-Finnish (FIN) AF: 0.0531 AC: 2837 AN: 53420

Middle Eastern (MID) AF: 0.0715 AC: 412 AN: 5766

European-Non Finnish (NFE) AF: 0.0657 AC: 73079 AN: 1111948

Other (OTH) AF: 0.0644 AC: 3891 AN: 60392

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

African (AFR) AF: 0.0973 AC: 4035 AN: 41464

American (AMR) AF: 0.0668 AC: 1021 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5174

South Asian (SAS) AF: 0.0785 AC: 379 AN: 4826

European-Finnish (FIN) AF: 0.0526 AC: 558 AN: 10600

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0670 AC: 4556 AN: 68006

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.0704 Hom.: 268

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

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Tyrosinemia type II Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.58
DANN	Benign	0.76
PhyloP100		-6.6
Mutation Taster		=99/1	polymorphism (auto)

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