Variant chr9-136380842-G-C 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.2397C>G(p.His799Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,591,998 control chromosomes in the GnomAD database, including 150,875 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 0.42 ( 13570 hom., cov: 33)

Exomes 𝑓: 0.43 ( 137305 hom. )

Consequence

SNAPC4
NM_003086.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.214

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=1.2946129E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC4	NM_003086.4 linkuse as main transcript	c.2397C>G	p.His799Gln	missense_variant	20/24	ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SNAPC4	ENST00000684778.1 linkuse as main transcript	c.2397C>G	p.His799Gln	missense_variant	20/24		NM_003086.4	P1
SNAPC4	ENST00000298532.2 linkuse as main transcript	c.2397C>G	p.His799Gln	missense_variant	19/23	1		P1
SNAPC4	ENST00000637388.2 linkuse as main transcript	c.2397C>G	p.His799Gln	missense_variant	20/24	5		P1
SNAPC4	ENST00000689006.1 linkuse as main transcript	c.*1610C>G		3_prime_UTR_variant, NMD_transcript_variant	20/24

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63698

AN:

151930

Hom.:

13544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.438

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.429

AC:

106574

AN:

248460

Hom.:

23621

AF XY:

0.420

AC XY:

56658

AN XY:

134880

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.443

Gnomad OTH exome

AF:

0.447

GnomAD4 exome

AF:

0.432

AC:

622298

AN:

1439950

Hom.:

137305

Cov.:

AF XY:

0.428

AC XY:

307188

AN XY:

717466

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.447

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.419

AC:

63782

AN:

152048

Hom.:

13570

Cov.:

AF XY:

0.417

AC XY:

31015

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.517

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.438

Gnomad4 OTH

AF:

0.420

Alfa

AF:

0.438

Hom.:

4511

Bravo

AF:

0.424

TwinsUK

AF:

0.446

AC:

1654

ALSPAC

AF:

0.447

AC:

1723

ESP6500AA

AF:

0.364

AC:

1604

ESP6500EA

AF:

0.443

AC:

3805

ExAC

AF:

0.421

AC:

51061

Asia WGS

AF:

0.395

AC:

1374

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.20

MetaRNN

Benign

0.00013

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

2.6

REVEL

Benign

0.088

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.039

MutPred

0.29

Gain of helix (P = 0.0143);

ClinPred

0.0060

GERP RS

4.2

Varity_R

0.023

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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