Genetic Variant SFN:c.*401_*406dupTGTGTG (chr1-26864330-G-GGTGTGT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_006142.5(SFN):c.*401_*406dupTGTGTG 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 0.0090 ( 11 hom., cov: 0)

Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

SFN
NM_006142.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

Publications

4 publications found

Variant links:

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]

SFN links:

ENSG00000304862 (HGNC:):

ENSG00000304862 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00895 (1290/144098) while in subpopulation SAS AF = 0.0194 (86/4438). AF 95% confidence interval is 0.0161. There are 11 homozygotes in GnomAd4. There are 615 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 1290 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_406dupTGTGTG		3_prime_UTR	Exon 1 of 1	NP_006133.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SFN	ENST00000339276.6	TSL:6 MANE Select	c.401_406dupTGTGTG	3_prime_UTR	Exon 1 of 1	ENSP00000340989.4
ENSG00000304862	ENST00000806706.1		n.93+707_93+712dupACACAC	intron	N/A
ENSG00000304862	ENST00000806707.1		n.80+707_80+712dupACACAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1294

AN:

144016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00550

Gnomad AMI

AF:

0.00116

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00176

Gnomad EAS

AF:

0.0107

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.00671

Gnomad MID

AF:

0.00993

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0118

GnomAD4 exome

AF:

0.00232

AC:

136

AN:

58526

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

AN XY:

29670

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

2158

American (AMR)

AF:

0.00145

AC:

AN:

2062

Ashkenazi Jewish (ASJ)

AF:

0.000861

AC:

AN:

1162

East Asian (EAS)

AF:

0.00

AC:

AN:

2074

South Asian (SAS)

AF:

0.00108

AC:

AN:

5554

European-Finnish (FIN)

AF:

0.00532

AC:

AN:

15410

Middle Eastern (MID)

AF:

0.00439

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.00154

AC:

AN:

27330

Other (OTH)

AF:

0.000392

AC:

AN:

2548

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.378

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00895

AC:

1290

AN:

144098

Hom.:

Cov.:

AF XY:

0.00884

AC XY:

615

AN XY:

69568

show subpopulations

African (AFR)

AF:

0.00551

AC:

214

AN:

38818

American (AMR)

AF:

0.0107

AC:

154

AN:

14400

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

3418

East Asian (EAS)

AF:

0.0103

AC:

AN:

4654

South Asian (SAS)

AF:

0.0194

AC:

AN:

4438

European-Finnish (FIN)

AF:

0.00671

AC:

AN:

9240

Middle Eastern (MID)

AF:

0.00360

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0105

AC:

695

AN:

66030

Other (OTH)

AF:

0.0117

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00419

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over