rs3847968

Positions:

• chr12-120293066-G-A
• chr12-120293066-G-C
• chr12-120293066-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_006719309.5(SIRT4):​c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 124,676 control chromosomes in the GnomAD database, including 359 homozygotes. 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: 𝑓 0.069 (359 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIRT4 XM_006719309.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

SIRT4 (HGNC:):

RNU4-1 (HGNC:10192): (RNA, U4 small nuclear 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT4	XM_006719309.5	c.-230G>A		5_prime_UTR_variant	1/4		XP_006719372.1
SIRT4	NM_001385733.1	c.-2+124G>A		intron_variant			NP_001372662.1
SIRT4	NM_001385735.1	c.-2+124G>A		intron_variant			NP_001372664.1
RNU4-1	NR_003925.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNU4-1	ENST00000363925.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 8600 AN: 124556 Hom.: 358 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.0591

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0255

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0690

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0692 AC: 8622 AN: 124676 Hom.: 359 Cov.: 33 AF XY: 0.0741 AC XY: 4444 AN XY: 59978

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0255

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0943

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0469 Hom.: 214

Bravo AF: 0.0622

Asia WGS AF: 0.0710 AC: 246 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0020
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3847968; hg19: chr12-120730869;