9-136377751-G-T

Variant names:

• chr9-136377751-G-T
• rs377237409
• NM_003086.4:c.4076C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003086.4(SNAPC4):​c.4076C>A​(p.Pro1359Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,182 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1359L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNAPC4 NM_003086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4076C>A	p.Pro1359Gln	missense	Exon 22 of 24	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.4076C>A	p.Pro1359Gln	missense	Exon 22 of 24	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.3992C>A	p.Pro1331Gln	missense	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.4076C>A	p.Pro1359Gln	missense	Exon 22 of 24	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.4076C>A	p.Pro1359Gln	missense	Exon 21 of 23	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.4076C>A	p.Pro1359Gln	missense	Exon 22 of 24	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243454 AF XY: 0.00000753

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458182 Hom.: 0 Cov.: 42 AF XY: 0.00000138 AC XY: 1 AN XY: 725054

African (AFR) AF: 0.0000299 AC: 1 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110520

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.51		Loss of glycosylation at P1359 (P = 0.1346)
MVP		0.86
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.42
gMVP		0.54
Mutation Taster		=73/27	polymorphism

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: rs377237409; hg19: chr9-139272203;