rs75855289

Variant names:

• chr16-71566868-A-T
• rs75855289
• NM_000353.3:c.*1276T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-71566868-A-T
• chr16-71566868-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000353.3(TAT):​c.*1276T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00879 in 141,806 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (9 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TAT NM_000353.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.565
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-71566868-A-T is Benign according to our data. Variant chr16-71566868-A-T is described in ClinVar as Benign. ClinVar VariationId is 320386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00879 (1247/141806) while in subpopulation AFR AF = 0.0295 (1145/38806). AF 95% confidence interval is 0.0281. There are 9 homozygotes in GnomAd4. There are 592 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.*1276T>A		3_prime_UTR	Exon 12 of 12	NP_000344.1	P17735
	TAT-AS1	NR_103851.1		n.284+667A>T		intron	N/A
	TAT-AS1	NR_103852.1		n.258+667A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	ENST00000355962.5	TSL:1 MANE Select	c.*1276T>A		3_prime_UTR	Exon 12 of 12	ENSP00000348234.4	P17735
	TAT	ENST00000895695.1		c.*1276T>A		3_prime_UTR	Exon 12 of 12	ENSP00000565754.1
	TAT	ENST00000895697.1		c.*1276T>A		3_prime_UTR	Exon 11 of 11	ENSP00000565756.1

Frequencies

GnomAD3 genomes AF: 0.00873 AC: 1238 AN: 141786 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00487

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00686

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00879 AC: 1247 AN: 141806 Hom.: 9 Cov.: 32 AF XY: 0.00858 AC XY: 592 AN XY: 68984

African (AFR) AF: 0.0295 AC: 1145 AN: 38806

American (AMR) AF: 0.00487 AC: 69 AN: 14168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.000874 AC: 4 AN: 4576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000250 AC: 16 AN: 64012

Other (OTH) AF: 0.00681 AC: 13 AN: 1910

Alfa AF: 0.00397 Hom.: 0

Bravo AF: 0.00949

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Tyrosinemia type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.28
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

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: rs75855289; hg19: chr16-71600771;