Genetic Variant NM_006142.5:c.*405_*406delTG (chr1-26864330-GGT-G) – 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.*405_*406delTG 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

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 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 5403 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.405_406delTG		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.405_406delTG	3_prime_UTR	Exon 1 of 1	ENSP00000340989.4
ENSG00000304862	ENST00000806706.1		n.93+711_93+712delAC	intron	N/A
ENSG00000304862	ENST00000806707.1		n.80+711_80+712delAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0375

AC:

5398

AN:

143888

Hom.:

124

Cov.:

show subpopulations

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.:

AF XY:

0.0208

AC XY:

614

AN XY:

29488

show subpopulations

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

African (AFR)

AF:

0.0116

AC:

AN:

2156

American (AMR)

AF:

0.0199

AC:

AN:

2058

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

1158

East Asian (EAS)

AF:

0.00964

AC:

AN:

2074

South Asian (SAS)

AF:

0.00721

AC:

AN:

5550

European-Finnish (FIN)

AF:

0.0396

AC:

599

AN:

15126

Middle Eastern (MID)

AF:

0.0175

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0158

AC:

430

AN:

27284

Other (OTH)

AF:

0.0114

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.353

Heterozygous variant carriers

166

249

332

415

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:

0.0375

AC:

5403

AN:

143968

Hom.:

124

Cov.:

AF XY:

0.0366

AC XY:

2540

AN XY:

69492

show subpopulations

African (AFR)

AF:

0.0510

AC:

1976

AN:

38776

American (AMR)

AF:

0.0530

AC:

762

AN:

14390

Ashkenazi Jewish (ASJ)

AF:

0.0322

AC:

110

AN:

3416

East Asian (EAS)

AF:

0.0531

AC:

247

AN:

4648

South Asian (SAS)

AF:

0.0428

AC:

190

AN:

4438

European-Finnish (FIN)

AF:

0.0111

AC:

102

AN:

9208

Middle Eastern (MID)

AF:

0.0468

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0291

AC:

1922

AN:

65994

Other (OTH)

AF:

0.0383

AC:

AN:

1960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

246

492

739

985

1231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0166

Hom.:

273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.022

Mutation Taster

=100/0

polymorphism

(source)

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

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NM_006142.5:c.405_406delTG

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