NM_003086.4:c.4174G>A

Variant names:

• chr9-136377653-C-T
• rs1314004223
• NM_003086.4:c.4174G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003086.4(SNAPC4):​c.4174G>A​(p.Val1392Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNAPC4 NM_003086.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033944547).

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.4174G>A	p.Val1392Ile	missense	Exon 22 of 24	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.4174G>A	p.Val1392Ile	missense	Exon 22 of 24	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.4090G>A	p.Val1364Ile	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.4174G>A	p.Val1392Ile	missense	Exon 22 of 24	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.4174G>A	p.Val1392Ile	missense	Exon 21 of 23	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.4174G>A	p.Val1392Ile	missense	Exon 22 of 24	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450298 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 720090

African (AFR) AF: 0.00 AC: 0 AN: 33214

American (AMR) AF: 0.00 AC: 0 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25632

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00 AC: 0 AN: 85208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105604

Other (OTH) AF: 0.00 AC: 0 AN: 59814

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.1
DANN	Benign	0.75
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.23
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.0070
Sift	Benign	0.20	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.049
MutPred		0.11		Gain of loop (P = 0.0851)
MVP		0.27
ClinPred		0.024	T
GERP RS		-1.2
Varity_R		0.029
gMVP		0.061
Mutation Taster		=95/5	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: rs1314004223; hg19: chr9-139272105;