rs3812565

Variant names:

• chr9-136378050-T-C
• rs3812565
• NM_003086.4:c.3777A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003086.4(SNAPC4):​c.3777A>G​(p.Leu1259Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,576,956 control chromosomes in the GnomAD database, including 115,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10086 hom., cov: 33)
  • Exomes 𝑓: 0.38 (105757 hom.)
• Consequence: SNAPC4 NM_003086.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.79
• Publications: 32 publications found

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: STRONG, MODERATE Submitted by: PanelApp Australia, Baylor College of Medicine Research Center, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-136378050-T-C is Benign according to our data. Variant chr9-136378050-T-C is described in ClinVar as Benign. ClinVar VariationId is 402490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	NM_003086.4	MANE Select	c.3777A>G	p.Leu1259Leu	synonymous	Exon 22 of 24	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.3777A>G	p.Leu1259Leu	synonymous	Exon 22 of 24	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.3693A>G	p.Leu1231Leu	synonymous	Exon 22 of 24	NP_001381131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	ENST00000684778.1	MANE Select	c.3777A>G	p.Leu1259Leu	synonymous	Exon 22 of 24	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.3777A>G	p.Leu1259Leu	synonymous	Exon 21 of 23	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.3777A>G	p.Leu1259Leu	synonymous	Exon 22 of 24	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54503 AN: 151404 Hom.: 10057 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.337

GnomAD2 exomes AF: 0.372 AC: 68165 AN: 183368 AF XY: 0.360

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.380 AC: 542361 AN: 1425434 Hom.: 105757 Cov.: 46 AF XY: 0.376 AC XY: 265730 AN XY: 706510

African (AFR) AF: 0.303 AC: 9868 AN: 32582

American (AMR) AF: 0.523 AC: 20512 AN: 39232

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8151 AN: 25342

East Asian (EAS) AF: 0.220 AC: 8328 AN: 37872

South Asian (SAS) AF: 0.279 AC: 23132 AN: 83026

European-Finnish (FIN) AF: 0.369 AC: 17977 AN: 48710

Middle Eastern (MID) AF: 0.246 AC: 1268 AN: 5164

European-Non Finnish (NFE) AF: 0.395 AC: 431956 AN: 1094744

Other (OTH) AF: 0.360 AC: 21169 AN: 58762

GnomAD4 genome AF: 0.360 AC: 54584 AN: 151522 Hom.: 10086 Cov.: 33 AF XY: 0.358 AC XY: 26489 AN XY: 74026

African (AFR) AF: 0.312 AC: 12869 AN: 41276

American (AMR) AF: 0.466 AC: 7110 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1132 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1011 AN: 5104

South Asian (SAS) AF: 0.279 AC: 1336 AN: 4796

European-Finnish (FIN) AF: 0.368 AC: 3872 AN: 10524

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26139 AN: 67788

Other (OTH) AF: 0.338 AC: 711 AN: 2106

Alfa AF: 0.377 Hom.: 3667

Bravo AF: 0.363

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.74
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3812565; hg19: chr9-139272502; COSMIC: COSV53731140; COSMIC: COSV53731140;