9-136376424-G-A

Variant names:

• chr9-136376424-G-A
• rs3812561
• NM_003086.4:c.4342C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.040 (151 hom., cov: 34)
  • Exomes 𝑓: 0.034 (1072 hom.)
• Consequence: SNAPC4 NM_003086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SNAPC4	NM_003086.4	c.4342C>T	p.Pro1448Ser	missense_variant	Exon 23 of 24	ENST00000684778.1	NP_003077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAPC4	ENST00000684778.1	c.4342C>T	p.Pro1448Ser	missense_variant	Exon 23 of 24		NM_003086.4	ENSP00000510559.1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6124 AN: 152198 Hom.: 150 Cov.: 34

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

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.: 31 AF XY: 0.0345 AC XY: 25068 AN XY: 726892

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.: 34 AF XY: 0.0405 AC XY: 3017 AN XY: 74474

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	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.57
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.030
Sift	Benign	0.30	T
Sift4G	Benign	0.096	T
Polyphen		0.021	B
Vest4		0.11
ClinPred		0.00092	T
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

Other links and lift over

dbSNP: rs3812561; hg19: chr9-139270876; COSMIC: COSV53733515; COSMIC: COSV53733515;