rs11145797

Variant names:

• chr9-136380580-G-A
• rs11145797
• NM_003086.4:c.2499+160C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-136380580-G-A
• chr9-136380580-G-C

Variant summary

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

The NM_003086.4(SNAPC4):​c.2499+160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,180 control chromosomes in the GnomAD database, including 1,764 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 0.15 (1764 hom., cov: 33)
• Consequence: SNAPC4 NM_003086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 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.2499+160C>T		intron	N/A	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.2499+160C>T		intron	N/A	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.2415+160C>T		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.2499+160C>T		intron	N/A	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.2499+160C>T		intron	N/A	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.2499+160C>T		intron	N/A	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22517 AN: 152062 Hom.: 1753 Cov.: 33

Gnomad AFR AF: 0.0986

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.148 AC: 22559 AN: 152180 Hom.: 1764 Cov.: 33 AF XY: 0.147 AC XY: 10959 AN XY: 74392

African (AFR) AF: 0.0989 AC: 4109 AN: 41532

American (AMR) AF: 0.196 AC: 3001 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1331 AN: 5172

South Asian (SAS) AF: 0.170 AC: 819 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10600

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10979 AN: 67962

Other (OTH) AF: 0.130 AC: 275 AN: 2110

Alfa AF: 0.159 Hom.: 263

Bravo AF: 0.151

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.69
PhyloP100		-2.2
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: rs11145797; hg19: chr9-139275032; COSMIC: COSV53738979; COSMIC: COSV53738979;