10-67888811-T-G

Variant names:

• chr10-67888811-T-G
• rs2236318
• NM_012238.5:c.548-71T>G

Variant summary

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

The NM_012238.5(SIRT1):​c.548-71T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,361,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

Genes affected

SIRT1 (HGNC:14929): (sirtuin 1) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

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=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.548-71T>G		intron_variant	Intron 2 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-97+1278T>G		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-487-71T>G		intron_variant	Intron 2 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.548-71T>G		intron_variant	Intron 2 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-97+1278T>G		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.333+1278T>G		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.337-71T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1361762 Hom.: 0 AF XY: 0.00000149 AC XY: 1 AN XY: 670712

African (AFR) AF: 0.00 AC: 0 AN: 30320

American (AMR) AF: 0.00 AC: 0 AN: 31496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21502

East Asian (EAS) AF: 0.00 AC: 0 AN: 38842

South Asian (SAS) AF: 0.00 AC: 0 AN: 70726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059694

Other (OTH) AF: 0.0000178 AC: 1 AN: 56184

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		1.3

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: rs2236318; hg19: chr10-69648569;