chr16-71575953-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.

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.309G>A	p.Ser103Ser	synonymous	Exon 3 of 12	NP_000344.1	P17735

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	ENST00000355962.5	TSL:1 MANE Select	c.309G>A	p.Ser103Ser	synonymous	Exon 3 of 12	ENSP00000348234.4	P17735
	TAT	ENST00000566010.1	TSL:1	n.559G>A		non_coding_transcript_exon	Exon 2 of 2
	TAT	ENST00000895695.1		c.309G>A	p.Ser103Ser	synonymous	Exon 3 of 12	ENSP00000565754.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Tyrosinemia type II (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;