rs1314004223

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-136377653-C-G
• chr9-136377653-C-T

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>C​(p.Val1392Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,450,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. V1392I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SNAPC4 NM_003086.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.033134073).

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>C	p.Val1392Leu	missense	Exon 22 of 24	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.4174G>C	p.Val1392Leu	missense	Exon 22 of 24	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.4090G>C	p.Val1364Leu	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>C	p.Val1392Leu	missense	Exon 22 of 24	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.4174G>C	p.Val1392Leu	missense	Exon 21 of 23	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.4174G>C	p.Val1392Leu	missense	Exon 22 of 24	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 242932 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000124 AC: 18 AN: 1450298 Hom.: 0 Cov.: 42 AF XY: 0.0000125 AC XY: 9 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: 0.0000390 AC: 1 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: 0.0000154 AC: 17 AN: 1105604

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.73
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.23
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.021
Sift	Benign	0.23	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.10		Loss of sheet (P = 0.0457)
MVP		0.23
ClinPred		0.027	T
GERP RS		-1.2
Varity_R		0.040
gMVP		0.093
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;