dbSNP rs10781507: SNAPC4:p.Ser1407Arg (chr9-136377606-A-C) – 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_003086.4(SNAPC4):c.4221T>G(p.Ser1407Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1407S) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SNAPC4
NM_003086.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.265

Publications

47 publications found

Variant links:

Genes affected

SNAPC4 (HGNC:11137): (small nuclear RNA activating complex polypeptide 4) This gene encodes the largest subunit of the small nuclear RNA-activating protein (SNAP) complex. The encoded protein contains a Myb DNA-binding domain, and is essential for RNA polymerase II and III polymerase transcription from small nuclear RNA promoters. A mutation in this gene is associated with ankylosing spondylitis. [provided by RefSeq, Jul 2016]

SNAPC4 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
Inheritance: AR Classification: MODERATE Submitted by: Baylor College of Medicine Research Center, G2P

SNAPC4 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=0.05219549).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003086.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNAPC4	NM_003086.4	MANE Select	c.4221T>G	p.Ser1407Arg	missense	Exon 22 of 24	NP_003077.2
SNAPC4	NM_001394201.1		c.4221T>G	p.Ser1407Arg	missense	Exon 22 of 24	NP_001381130.1
SNAPC4	NM_001394202.1		c.4137T>G	p.Ser1379Arg	missense	Exon 22 of 24	NP_001381131.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNAPC4	ENST00000684778.1	MANE Select	c.4221T>G	p.Ser1407Arg	missense	Exon 22 of 24	ENSP00000510559.1
SNAPC4	ENST00000298532.2	TSL:1	c.4221T>G	p.Ser1407Arg	missense	Exon 21 of 23	ENSP00000298532.2
SNAPC4	ENST00000637388.2	TSL:5	c.4221T>G	p.Ser1407Arg	missense	Exon 22 of 24	ENSP00000490037.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391460

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31234

American (AMR)

AF:

0.00

AC:

AN:

34904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21900

East Asian (EAS)

AF:

0.00

AC:

AN:

38816

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5430

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074492

Other (OTH)

AF:

0.00

AC:

AN:

57156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

11809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.33

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0046

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.45

M_CAP

Benign

0.018

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

-0.27

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.2

REVEL

Benign

0.030

Sift

Uncertain

0.014

Sift4G

Benign

0.070

Polyphen

0.24

Vest4

0.081

MutPred

0.18

Gain of helix (P = 0.0082)

MVP

0.067

ClinPred

0.12

GERP RS

-4.8

Varity_R

0.12

gMVP

0.097

Mutation Taster

=89/11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over