Genetic Variant NM_001130003.2:c.700C>G (chr3-63615323-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130003.2(SYNPR):c.700C>G(p.Pro234Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P234S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SYNPR
NM_001130003.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.699

Publications

0 publications found

Variant links:

Genes affected

SYNPR (HGNC:16507): (synaptoporin) Predicted to be located in neuron projection and synaptic vesicle. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYNPR links:

SYNPR-AS1 (HGNC:40774): (SYNPR antisense RNA 1)

SYNPR-AS1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0297347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130003.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPR	NM_001130003.2	MANE Select	c.700C>G	p.Pro234Ala	missense	Exon 6 of 6	NP_001123475.1	Q8TBG9-2
	SYNPR	NM_144642.5		c.640C>G	p.Pro214Ala	missense	Exon 5 of 5	NP_653243.1	Q8TBG9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNPR	ENST00000478300.6	TSL:1 MANE Select	c.700C>G	p.Pro234Ala	missense	Exon 6 of 6	ENSP00000418994.1	Q8TBG9-2
SYNPR	ENST00000295894.9	TSL:1	c.640C>G	p.Pro214Ala	missense	Exon 5 of 5	ENSP00000295894.5	Q8TBG9-1
SYNPR	ENST00000450542.6	TSL:1	c.*470C>G		3_prime_UTR	Exon 5 of 5	ENSP00000402121.2	F8WE43

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111822

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.011

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.81

M_CAP

Benign

0.0062

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.73

PhyloP100

0.70

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.74

REVEL

Benign

0.028

Sift

Benign

0.82

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.11

MutPred

0.17

Loss of glycosylation at P225 (P = 0.0304)

MVP

0.040

MPC

0.060

ClinPred

0.047

GERP RS

1.4

Varity_R

0.040

gMVP

0.46

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over