Genetic Variant NM_006142.5:c.*395_*406delTGTGTGTGTGTG (chr1-26864330-GGTGTGTGTGTGT-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_006142.5(SFN):c.*395_*406delTGTGTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 202,588 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SFN
NM_006142.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 6 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.395_406delTGTGTGTGTGTG		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.395_406delTGTGTGTGTGTG	3_prime_UTR	Exon 1 of 1	ENSP00000340989.4
ENSG00000304862	ENST00000806706.1		n.93+701_93+712delACACACACACAC	intron	N/A
ENSG00000304862	ENST00000806707.1		n.80+701_80+712delACACACACACAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000417

AC:

AN:

144034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000695

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000214

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

58554

Hom.:

AF XY:

0.0000337

AC XY:

AN XY:

29690

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:

0.00

AC:

AN:

2062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1164

East Asian (EAS)

AF:

0.00

AC:

AN:

2074

South Asian (SAS)

AF:

0.00

AC:

AN:

5554

European-Finnish (FIN)

AF:

0.0000648

AC:

AN:

15434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

27332

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: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000417

AC:

AN:

144034

Hom.:

Cov.:

AF XY:

0.0000576

AC XY:

AN XY:

69478

show subpopulations

African (AFR)

AF:

0.0000517

AC:

AN:

38720

American (AMR)

AF:

0.0000695

AC:

AN:

14386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.000214

AC:

AN:

4668

South Asian (SAS)

AF:

0.00

AC:

AN:

4452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

66044

Other (OTH)

AF:

0.00

AC:

AN:

1942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

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

Publications

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NM_006142.5:c.395_406delTGTGTGTGTGTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over