Genetic Variant CCSER1:p.Gly288Ser (chr4-90309146-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145065.2(CCSER1):c.862G>A(p.Gly288Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,798 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

CCSER1
NM_001145065.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Publications

0 publications found

Variant links:

Genes affected

CCSER1 (HGNC:29349): (coiled-coil serine rich protein 1)

CCSER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017123759).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145065.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCSER1	NM_001145065.2	MANE Select	c.862G>A	p.Gly288Ser	missense	Exon 2 of 11	NP_001138537.1	Q9C0I3-1
CCSER1	NM_001377987.1		c.862G>A	p.Gly288Ser	missense	Exon 2 of 10	NP_001364916.1
CCSER1	NM_207491.2		c.862G>A	p.Gly288Ser	missense	Exon 2 of 8	NP_997374.1	Q9C0I3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCSER1	ENST00000509176.6	TSL:1 MANE Select	c.862G>A	p.Gly288Ser	missense	Exon 2 of 11	ENSP00000425040.1	Q9C0I3-1
CCSER1	ENST00000432775.6	TSL:1	c.862G>A	p.Gly288Ser	missense	Exon 2 of 8	ENSP00000389283.2	Q9C0I3-2
CCSER1	ENST00000505073.5	TSL:1	n.862G>A		non_coding_transcript_exon	Exon 2 of 10	ENSP00000420964.1	E7EUW0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000133

AC:

AN:

248656

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000719

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111824

Other (OTH)

AF:

0.0000828

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000263

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41508

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000572

Hom.:

ExAC

AF:

0.000141

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.79

M_CAP

Benign

0.0071

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

2.8

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

REVEL

Benign

0.066

Sift

Benign

0.17

Sift4G

Benign

1.0

Polyphen

0.061

Vest4

0.26

MutPred

0.067

Loss of stability (P = 0.1009)

MVP

0.18

MPC

0.067

ClinPred

0.051

GERP RS

3.1

Varity_R

0.056

gMVP

0.21

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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