1-26864330-GGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGT

Variant names:

• chr1-26864330-GGTGTGT-G
• rs3065004
• NM_006142.5:c.*401_*406delTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006142.5(SFN):​c.*401_*406delTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00617 in 202,256 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: SFN NM_006142.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 4 publications found

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]

ENSG00000304862 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 596 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006142.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFN	NM_006142.5	MANE Select	c.*401_*406delTGTGTG		3_prime_UTR	Exon 1 of 1	NP_006133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFN	ENST00000339276.6	TSL:6 MANE Select	c.*401_*406delTGTGTG		3_prime_UTR	Exon 1 of 1	ENSP00000340989.4
	ENSG00000304862	ENST00000806706.1		n.93+707_93+712delACACAC		intron	N/A
	ENSG00000304862	ENST00000806707.1		n.80+707_80+712delACACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00408 AC: 588 AN: 143960 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00697

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00250

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.00664

Gnomad SAS AF: 0.00247

Gnomad FIN AF: 0.00163

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.00317

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.0112 AC: 651 AN: 58216 Hom.: 0 AF XY: 0.0112 AC XY: 332 AN XY: 29522

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00139 AC: 3 AN: 2158

American (AMR) AF: 0.00632 AC: 13 AN: 2058

Ashkenazi Jewish (ASJ) AF: 0.00861 AC: 10 AN: 1162

East Asian (EAS) AF: 0.00289 AC: 6 AN: 2074

South Asian (SAS) AF: 0.00288 AC: 16 AN: 5552

European-Finnish (FIN) AF: 0.0248 AC: 376 AN: 15158

Middle Eastern (MID) AF: 0.00446 AC: 1 AN: 224

European-Non Finnish (NFE) AF: 0.00762 AC: 208 AN: 27290

Other (OTH) AF: 0.00709 AC: 18 AN: 2540

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00414 AC: 596 AN: 144040 Hom.: 2 Cov.: 0 AF XY: 0.00395 AC XY: 275 AN XY: 69538

African (AFR) AF: 0.00714 AC: 277 AN: 38820

American (AMR) AF: 0.00250 AC: 36 AN: 14398

Ashkenazi Jewish (ASJ) AF: 0.000585 AC: 2 AN: 3416

East Asian (EAS) AF: 0.00666 AC: 31 AN: 4654

South Asian (SAS) AF: 0.00270 AC: 12 AN: 4440

European-Finnish (FIN) AF: 0.00163 AC: 15 AN: 9212

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.00317 AC: 209 AN: 66002

Other (OTH) AF: 0.00663 AC: 13 AN: 1960

Alfa AF: 0.00 Hom.: 273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3065004; hg19: chr1-27190821;