Variant rs3812561 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003086.4(SNAPC4):c.4342C>T(p.Pro1448Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 1,613,488 control chromosomes in the GnomAD database, including 1,223 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.040 ( 151 hom., cov: 34)

Exomes 𝑓: 0.034 ( 1072 hom. )

Consequence

SNAPC4
NM_003086.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.285

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015933514).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC4	NM_003086.4 linkuse as main transcript	c.4342C>T	p.Pro1448Ser	missense_variant	23/24	ENST00000684778.1	NP_003077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SNAPC4	ENST00000684778.1 linkuse as main transcript	c.4342C>T	p.Pro1448Ser	missense_variant	23/24		NM_003086.4	ENSP00000510559	P1
SNAPC4	ENST00000298532.2 linkuse as main transcript	c.4342C>T	p.Pro1448Ser	missense_variant	22/23	1		ENSP00000298532	P1
SNAPC4	ENST00000637388.2 linkuse as main transcript	c.4342C>T	p.Pro1448Ser	missense_variant	23/24	5		ENSP00000490037	P1
SNAPC4	ENST00000689006.1 linkuse as main transcript	c.*3555C>T		3_prime_UTR_variant, NMD_transcript_variant	23/24			ENSP00000509362

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6124

AN:

152198

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0289

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0542

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0337

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0398

AC:

10003

AN:

251038

Hom.:

285

AF XY:

0.0396

AC XY:

5380

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0515

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.0422

Gnomad FIN exome

AF:

0.0438

Gnomad NFE exome

AF:

0.0338

Gnomad OTH exome

AF:

0.0357

GnomAD4 exome

AF:

0.0343

AC:

50061

AN:

1461172

Hom.:

1072

Cov.:

AF XY:

0.0345

AC XY:

25068

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0303

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.0410

Gnomad4 FIN exome

AF:

0.0455

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.0373

GnomAD4 genome

AF:

0.0403

AC:

6134

AN:

152316

Hom.:

151

Cov.:

AF XY:

0.0405

AC XY:

3017

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0494

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0289

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.0536

Gnomad4 FIN

AF:

0.0454

Gnomad4 NFE

AF:

0.0338

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0329

Hom.:

201

Bravo

AF:

0.0374

TwinsUK

AF:

0.0316

AC:

117

ALSPAC

AF:

0.0293

AC:

113

ESP6500AA

AF:

0.0504

AC:

222

ESP6500EA

AF:

0.0314

AC:

270

ExAC

AF:

0.0406

AC:

4924

Asia WGS

AF:

0.105

AC:

364

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.1

DANN

Benign

0.57

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.59

REVEL

Benign

0.030

Sift

Benign

0.30

Sift4G

Benign

0.096

Polyphen

0.021

Vest4

0.11

ClinPred

0.00092

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.074

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over