Genetic Variant SERGEF:p.Ser327Ser (chr11-17959500-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_012139.4(SERGEF):c.981G>A(p.Ser327Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,612,984 control chromosomes in the GnomAD database, including 305,832 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35541 hom., cov: 31)

Exomes 𝑓: 0.60 ( 270291 hom. )

Consequence

SERGEF
NM_012139.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.12

Publications

25 publications found

Variant links:

Genes affected

SERGEF (HGNC:17499): (secretion regulating guanine nucleotide exchange factor) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in negative regulation of protein secretion. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SERGEF links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.076).

BP7

Synonymous conserved (PhyloP=-3.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERGEF	NM_012139.4 link	c.981G>A	p.Ser327Ser	synonymous_variant	Exon 9 of 11	ENST00000265965.10	NP_036271.1	Q9UGK8-1A8K8C1
SERGEF	NR_104040.2 link	n.1018G>A		non_coding_transcript_exon_variant	Exon 9 of 12
SERGEF	NR_104041.2 link	n.881+29097G>A		intron_variant	Intron 8 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10 link	c.981G>A	p.Ser327Ser	synonymous_variant	Exon 9 of 11	1	NM_012139.4	ENSP00000265965.5		Q9UGK8-1

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

102012

AN:

151926

Hom.:

35492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.480

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.651

GnomAD2 exomes

AF:

0.601

AC:

150615

AN:

250788

AF XY:

0.601

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.543

Gnomad ASJ exome

AF:

0.481

Gnomad EAS exome

AF:

0.494

Gnomad FIN exome

AF:

0.552

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.605

AC:

883764

AN:

1460940

Hom.:

270291

Cov.:

AF XY:

0.606

AC XY:

440111

AN XY:

726828

show subpopulations

African (AFR)

AF:

0.879

AC:

29428

AN:

33472

American (AMR)

AF:

0.546

AC:

24417

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

12544

AN:

26128

East Asian (EAS)

AF:

0.470

AC:

18652

AN:

39694

South Asian (SAS)

AF:

0.654

AC:

56368

AN:

86206

European-Finnish (FIN)

AF:

0.554

AC:

29607

AN:

53402

Middle Eastern (MID)

AF:

0.623

AC:

3593

AN:

5766

European-Non Finnish (NFE)

AF:

0.605

AC:

672325

AN:

1111212

Other (OTH)

AF:

0.610

AC:

36830

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16327

32655

48982

65310

81637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18260

36520

54780

73040

91300

<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:

0.672

AC:

102123

AN:

152044

Hom.:

35541

Cov.:

AF XY:

0.666

AC XY:

49492

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.873

AC:

36237

AN:

41516

American (AMR)

AF:

0.599

AC:

9137

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

1662

AN:

3466

East Asian (EAS)

AF:

0.502

AC:

2593

AN:

5166

South Asian (SAS)

AF:

0.667

AC:

3211

AN:

4814

European-Finnish (FIN)

AF:

0.559

AC:

5903

AN:

10558

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.607

AC:

41231

AN:

67950

Other (OTH)

AF:

0.655

AC:

1379

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1609

3217

4826

6434

8043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.618

Hom.:

57756

Bravo

AF:

0.679

Asia WGS

AF:

0.626

AC:

2179

AN:

3478

EpiCase

AF:

0.608

EpiControl

AF:

0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.16

(source)

DANN

Benign

0.65

PhyloP100

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over