dbSNP rs771179017: CCSER2:p.Asn339Thr (chr10-84372068-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001284240.2(CCSER2):c.1016A>C(p.Asn339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CCSER2
NM_001284240.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

CCSER2 (HGNC:29197): (coiled-coil serine rich protein 2) Predicted to enable microtubule binding activity. Predicted to act upstream of or within microtubule bundle formation. Predicted to be located in cytoplasm and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CCSER2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17396763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSER2	NM_001284240.2 link	c.1016A>C	p.Asn339Thr	missense_variant	Exon 2 of 10	ENST00000372088.8	NP_001271169.1	Q9H7U1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCSER2	ENST00000372088.8 link	c.1016A>C	p.Asn339Thr	missense_variant	Exon 2 of 10	2	NM_001284240.2	ENSP00000361160.2	Q9H7U1-3
CCSER2	ENST00000359979.8 link	c.1016A>C	p.Asn339Thr	missense_variant	Exon 2 of 3	1		ENSP00000353068.4	Q9H7U1-2
CCSER2	ENST00000224756.12 link	c.1016A>C	p.Asn339Thr	missense_variant	Exon 2 of 11	5		ENSP00000224756.8	Q9H7U1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250336

AF XY:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111836

Other (OTH)

AF:

0.0000331

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 10, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1016A>C (p.N339T) alteration is located in exon 2 (coding exon 1) of the CCSER2 gene. This alteration results from a A to C substitution at nucleotide position 1016, causing the asparagine (N) at amino acid position 339 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

.;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

L;L;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

N;D;N

REVEL

Benign

0.032

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.86

P;D;P

Vest4

0.34

MutPred

0.14

Gain of phosphorylation at N339 (P = 0.0096);Gain of phosphorylation at N339 (P = 0.0096);Gain of phosphorylation at N339 (P = 0.0096);

MVP

0.64

MPC

0.45

ClinPred

0.57

GERP RS

5.7

Varity_R

0.057

gMVP

0.049

Mutation Taster

=85/15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

rs771179017

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over