chr9-136390000-A-G

Variant names:

• chr9-136390000-A-G
• rs11145835
• NM_003086.4:c.976-1409T>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.976-1409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,290 control chromosomes in the GnomAD database, including 998 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 0.10 (998 hom., cov: 32)
• Consequence: SNAPC4 NM_003086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 9 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: MODERATE Submitted by: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.172 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	NM_003086.4	MANE Select	c.976-1409T>C		intron	N/A	NP_003077.2
	SNAPC4	NM_001394201.1		c.976-1409T>C		intron	N/A	NP_001381130.1
	SNAPC4	NM_001394202.1		c.976-1409T>C		intron	N/A	NP_001381131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	ENST00000684778.1	MANE Select	c.976-1409T>C		intron	N/A	ENSP00000510559.1
	SNAPC4	ENST00000298532.2	TSL:1	c.976-1409T>C		intron	N/A	ENSP00000298532.2
	SNAPC4	ENST00000637388.2	TSL:5	c.976-1409T>C		intron	N/A	ENSP00000490037.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15933 AN: 152172 Hom.: 987 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.105 AC: 15965 AN: 152290 Hom.: 998 Cov.: 32 AF XY: 0.104 AC XY: 7738 AN XY: 74476

African (AFR) AF: 0.0398 AC: 1654 AN: 41564

American (AMR) AF: 0.177 AC: 2713 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3472

East Asian (EAS) AF: 0.135 AC: 700 AN: 5178

South Asian (SAS) AF: 0.115 AC: 555 AN: 4826

European-Finnish (FIN) AF: 0.0876 AC: 930 AN: 10616

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8706 AN: 68026

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.124 Hom.: 670

Bravo AF: 0.110

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		-0.22
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: rs11145835; hg19: chr9-139284452;