NM_000353.3:c.1068G>C

Variant names:

• chr16-71569911-C-G
• NM_000353.3:c.1068G>C
• TAT p.Ala356Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000353.3(TAT):​c.1068G>C​(p.Ala356Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A356A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAT NM_000353.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.001 with no splicing effect.

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.1068G>C	p.Ala356Ala	synonymous	Exon 10 of 12	NP_000344.1	P17735
	TAT-AS1	NR_103851.1		n.285-2109C>G		intron	N/A
	TAT-AS1	NR_103852.1		n.259-2109C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	ENST00000355962.5	TSL:1 MANE Select	c.1068G>C	p.Ala356Ala	synonymous	Exon 10 of 12	ENSP00000348234.4	P17735
	TAT	ENST00000895695.1		c.1068G>C	p.Ala356Ala	synonymous	Exon 10 of 12	ENSP00000565754.1
	TAT	ENST00000895697.1		c.1068G>C	p.Ala356Ala	synonymous	Exon 9 of 11	ENSP00000565756.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		0.0010

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-71603814;