rs1018491678

Variant names:

• chr16-71568146-A-G
• rs1018491678
• NM_000353.3:c.1363T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000353.3(TAT):​c.1363T>C​(p.Ter455Glnext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TAT NM_000353.3 stop_lost
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.25
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_000353.3 Downstream stopcodon found after 486 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAT	NM_000353.3	c.1363T>C	p.Ter455Glnext*?	stop_lost	Exon 12 of 12	ENST00000355962.5	NP_000344.1
TAT-AS1	NR_103851.1	n.284+1945A>G		intron_variant	Intron 2 of 2
TAT-AS1	NR_103852.1	n.258+1945A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAT	ENST00000355962.5	c.1363T>C	p.Ter455Glnext*?	stop_lost	Exon 12 of 12	1	NM_000353.3	ENSP00000348234.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Tyrosinemia type II Uncertain:1

Sep 20, 2017

Counsyl

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.89
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		5.3
Vest4		0.16
GERP RS		6.2

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: rs1018491678; hg19: chr16-71602049;