19-4182063-T-G

Variant names:

• chr19-4182063-T-G
• rs4807546
• NM_016539.4:c.66+411A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016539.4(SIRT6):​c.66+411A>C variant causes a intron 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIRT6 NM_016539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 24 publications found

Genes affected

SIRT6 (HGNC:14934): (sirtuin 6) This gene encodes a member of the sirtuin family of NAD-dependent enzymes that are implicated in cellular stress resistance, genomic stability, aging and energy homeostasis. The encoded protein is localized to the nucleus, exhibits ADP-ribosyl transferase and histone deacetylase activities, and plays a role in DNA repair, maintenance of telomeric chromatin, inflammation, lipid and glucose metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016539.4. 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
	SIRT6	NM_016539.4	MANE Select	c.66+411A>C		intron	N/A	NP_057623.2	Q8N6T7-1
	SIRT6	NM_001193285.3		c.66+411A>C		intron	N/A	NP_001180214.1	Q8N6T7-2
	SIRT6	NM_001321059.2		c.66+411A>C		intron	N/A	NP_001307988.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT6	ENST00000337491.7	TSL:1 MANE Select	c.66+411A>C		intron	N/A	ENSP00000337332.1	Q8N6T7-1
	SIRT6	ENST00000305232.10	TSL:1	c.66+411A>C		intron	N/A	ENSP00000305310.5	Q8N6T7-2
	SIRT6	ENST00000599365.5	TSL:1	n.66+411A>C		intron	N/A	ENSP00000473085.1	M0R0B2

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

Alfa AF: 0.00 Hom.: 5055

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.0
DANN	Benign	0.85
PhyloP100		-2.4
PromoterAI		-0.079	Neutral

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: rs4807546; hg19: chr19-4182060;