chr9-136376903-T-C

Variant names:

• chr9-136376903-T-C
• rs10781505
• NM_003086.4:c.4285-422A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003086.4(SNAPC4):​c.4285-422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,094 control chromosomes in the GnomAD database, including 13,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13447 hom., cov: 33)
• Consequence: SNAPC4 NM_003086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 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.4285-422A>G		intron	N/A	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.4285-422A>G		intron	N/A	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.4201-422A>G		intron	N/A	NP_001381131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	ENST00000684778.1	MANE Select	c.4285-422A>G		intron	N/A	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.4285-422A>G		intron	N/A	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.4285-422A>G		intron	N/A	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63223 AN: 151976 Hom.: 13426 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.416 AC: 63299 AN: 152094 Hom.: 13447 Cov.: 33 AF XY: 0.414 AC XY: 30814 AN XY: 74348

African (AFR) AF: 0.351 AC: 14582 AN: 41504

American (AMR) AF: 0.516 AC: 7885 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1599 AN: 5158

South Asian (SAS) AF: 0.337 AC: 1630 AN: 4830

European-Finnish (FIN) AF: 0.415 AC: 4395 AN: 10578

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30262 AN: 67960

Other (OTH) AF: 0.416 AC: 879 AN: 2112

Alfa AF: 0.420 Hom.: 5961

Bravo AF: 0.420

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.49
PhyloP100		-2.3
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: rs10781505; hg19: chr9-139271355; COSMIC: COSV53731763; COSMIC: COSV53731763;