Genetic Variant NM_006142.5:c.*399_*406delTGTGTGTG (chr1-26864330-GGTGTGTGT-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.*399_*406delTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 202,582 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00094 ( 0 hom. )

Consequence

SFN
NM_006142.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.70

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 65 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.399_406delTGTGTGTG		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.399_406delTGTGTGTG	3_prime_UTR	Exon 1 of 1	ENSP00000340989.4
ENSG00000304862	ENST00000806706.1		n.93+705_93+712delACACACAC	intron	N/A
ENSG00000304862	ENST00000806707.1		n.80+705_80+712delACACACAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000451

AC:

AN:

144030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00181

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000643

Gnomad SAS

AF:

0.000449

Gnomad FIN

AF:

0.000325

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000333

Gnomad OTH

AF:

0.00103

GnomAD4 exome

AF:

0.000941

AC:

AN:

58470

Hom.:

AF XY:

0.00108

AC XY:

AN XY:

29658

show subpopulations

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

African (AFR)

AF:

0.000927

AC:

AN:

2158

American (AMR)

AF:

0.00

AC:

AN:

2062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1162

East Asian (EAS)

AF:

0.00

AC:

AN:

2074

South Asian (SAS)

AF:

0.000720

AC:

AN:

5552

European-Finnish (FIN)

AF:

0.00130

AC:

AN:

15374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.000989

AC:

AN:

27312

Other (OTH)

AF:

0.000785

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: 0.291

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:

0.000451

AC:

AN:

144112

Hom.:

Cov.:

AF XY:

0.000402

AC XY:

AN XY:

69576

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

38820

American (AMR)

AF:

0.00181

AC:

AN:

14402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.000645

AC:

AN:

4654

South Asian (SAS)

AF:

0.000450

AC:

AN:

4442

European-Finnish (FIN)

AF:

0.000325

AC:

AN:

9240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000333

AC:

AN:

66036

Other (OTH)

AF:

0.00102

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

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

1.7

Splicing

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

Publications

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NM_006142.5:c.399_406delTGTGTGTG

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