1-26864330-GGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGT

Position:

• chr1-26864330-GGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006142.5(SFN):​c.*405_*406del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 202,142 control chromosomes in the GnomAD database, including 124 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (124 hom., cov: 0)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: SFN NM_006142.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

Genes affected

SFN (HGNC:10773): (stratifin) This gene encodes a cell cycle checkpoint protein. The encoded protein binds to translation and initiation factors and functions as a regulator of mitotic translation. In response to DNA damage this protein plays a role in preventing DNA errors during mitosis. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0375 (5403/143968) while in subpopulation EAS AF= 0.0531 (247/4648). AF 95% confidence interval is 0.0498. There are 124 homozygotes in gnomad4. There are 2540 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5403 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFN	NM_006142.5	c.*405_*406del		3_prime_UTR_variant	1/1	ENST00000339276.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFN	ENST00000339276.6	c.*405_*406del		3_prime_UTR_variant	1/1		NM_006142.5	P1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5398 AN: 143888 Hom.: 124 Cov.: 0

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.00698

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0322

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0381

GnomAD4 exome AF: 0.0207 AC: 1205 AN: 58174 Hom.: 0 AF XY: 0.0208 AC XY: 614 AN XY: 29488

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0199

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.00964

Gnomad4 SAS exome AF: 0.00721

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0375 AC: 5403 AN: 143968 Hom.: 124 Cov.: 0 AF XY: 0.0366 AC XY: 2540 AN XY: 69492

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.0530

Gnomad4 ASJ AF: 0.0322

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.0428

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3065004; hg19: chr1-27190821;