chr16-71568258-TCG-CCC

Variant names:

• chr16-71568258-TCG-CCC
• NM_000353.3:c.1249_1251delCGAinsGGG
• TAT p.Arg417Gly

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_000353.3(TAT):​c.1249_1251delCGAinsGGG​(p.Arg417Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R417Q) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAT NM_000353.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-71568259-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 550062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1249_1251delCGAinsGGG	p.Arg417Gly	missense	N/A	NP_000344.1	P17735
	TAT-AS1	NR_103851.1		n.284+2057_284+2059delTCGinsCCC		intron	N/A
	TAT-AS1	NR_103852.1		n.258+2057_258+2059delTCGinsCCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAT	ENST00000355962.5	TSL:1 MANE Select	c.1249_1251delCGAinsGGG	p.Arg417Gly	missense	N/A	ENSP00000348234.4	P17735
	TAT	ENST00000895695.1		c.1249_1251delCGAinsGGG	p.Arg417Gly	missense	N/A	ENSP00000565754.1
	TAT	ENST00000895697.1		c.1249_1251delCGAinsGGG	p.Arg417Gly	missense	N/A	ENSP00000565756.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

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: chr16-71602161;