rs139682930

chr9-136380838-C-Gchr9-136380838-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003086.4(SNAPC4):c.2401G>C(p.Asp801His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,603,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D801N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNAPC4 NM_003086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41938138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC4	NM_003086.4	c.2401G>C	p.Asp801His	missense_variant	20/24	ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.2401G>C	p.Asp801His	missense_variant	20/24		NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.2401G>C	p.Asp801His	missense_variant	19/23	1		P1
SNAPC4	ENST00000637388.2	c.2401G>C	p.Asp801His	missense_variant	20/24	5		P1
SNAPC4	ENST00000689006.1	c.*1614G>C		3_prime_UTR_variant, NMD_transcript_variant	20/24

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451096 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74322

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.095
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.45		Loss of solvent accessibility (P = 0.0169);
MVP		0.50
ClinPred		0.99	D
GERP RS		2.2
Varity_R		0.53
gMVP		0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs139682930; hg19: chr9-139275290;