Variant 9-136377676-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003086.4(SNAPC4):c.4151A>G(p.Gln1384Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,607,626 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

SNAPC4
NM_003086.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.709

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00782454).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC4	NM_003086.4 linkuse as main transcript	c.4151A>G	p.Gln1384Arg	missense_variant	22/24	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.4151A>G	p.Gln1384Arg	missense_variant	22/24		NM_003086.4	ENSP00000510559	P1
SNAPC4	ENST00000298532.2 linkuse as main transcript	c.4151A>G	p.Gln1384Arg	missense_variant	21/23	1		ENSP00000298532	P1
SNAPC4	ENST00000637388.2 linkuse as main transcript	c.4151A>G	p.Gln1384Arg	missense_variant	22/24	5		ENSP00000490037	P1
SNAPC4	ENST00000689006.1 linkuse as main transcript	c.*3364A>G		3_prime_UTR_variant, NMD_transcript_variant	22/24			ENSP00000509362

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000301

AC:

AN:

245508

Hom.:

AF XY:

0.000344

AC XY:

AN XY:

133578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000964

Gnomad FIN exome

AF:

0.0000937

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000403

AC:

586

AN:

1455376

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

292

AN XY:

723264

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000874

Gnomad4 FIN exome

AF:

0.000116

Gnomad4 NFE exome

AF:

0.000412

Gnomad4 OTH exome

AF:

0.000483

GnomAD4 genome

AF:

0.000407

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000219

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000256

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.4151A>G (p.Q1384R) alteration is located in exon 21 (coding exon 21) of the SNAPC4 gene. This alteration results from a A to G substitution at nucleotide position 4151, causing the glutamine (Q) at amino acid position 1384 to be replaced by an arginine (R). 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

0.059

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.041

DANN

Benign

0.27

DEOGEN2

Benign

0.00036

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.093

M_CAP

Benign

0.0040

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.13

REVEL

Benign

0.0070

Sift

Benign

0.14

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.033

MVP

0.16

ClinPred

0.018

GERP RS

-1.7

Varity_R

0.027

gMVP

0.061

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over