1-26864330-GGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr1-26864330-G-GGTGTGTGTGT
• rs3065004
• NM_006142.5:c.*397_*406dupTGTGTGTGTG

Variant summary

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

The NM_006142.5(SFN):​c.*397_*406dupTGTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: SFN NM_006142.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• 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 194 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.*397_*406dupTGTGTGTGTG		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.*397_*406dupTGTGTGTGTG		3_prime_UTR	Exon 1 of 1	ENSP00000340989.4
	ENSG00000304862	ENST00000806706.1		n.93+703_93+712dupACACACACAC		intron	N/A
	ENSG00000304862	ENST00000806707.1		n.80+703_80+712dupACACACACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 195 AN: 144030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000758

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00103

GnomAD4 exome AF: 0.0000683 AC: 4 AN: 58550 Hom.: 0 Cov.: 0 AF XY: 0.0000337 AC XY: 1 AN XY: 29688

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

African (AFR) AF: 0.00 AC: 0 AN: 2158

American (AMR) AF: 0.00 AC: 0 AN: 2062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1164

East Asian (EAS) AF: 0.00 AC: 0 AN: 2074

South Asian (SAS) AF: 0.00 AC: 0 AN: 5554

European-Finnish (FIN) AF: 0.000130 AC: 2 AN: 15434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.0000366 AC: 1 AN: 27328

Other (OTH) AF: 0.000392 AC: 1 AN: 2548

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000012246), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00135 AC: 194 AN: 144112 Hom.: 0 Cov.: 0 AF XY: 0.00119 AC XY: 83 AN XY: 69576

African (AFR) AF: 0.00126 AC: 49 AN: 38822

American (AMR) AF: 0.00208 AC: 30 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.000585 AC: 2 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 4654

South Asian (SAS) AF: 0.00 AC: 0 AN: 4442

European-Finnish (FIN) AF: 0.000758 AC: 7 AN: 9240

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

European-Non Finnish (NFE) AF: 0.00156 AC: 103 AN: 66034

Other (OTH) AF: 0.00102 AC: 2 AN: 1962

Alfa AF: 0.00 Hom.: 273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.022

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;