rs3812571

Variant names:

• chr9-136380842-G-A
• rs3812571
• NM_003086.4:c.2397C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-136380842-G-A
• chr9-136380842-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003086.4(SNAPC4):​c.2397C>T​(p.His799His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,030 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNAPC4 NM_003086.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 50 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.

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.2397C>T	p.His799His	synonymous	Exon 20 of 24	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.2397C>T	p.His799His	synonymous	Exon 20 of 24	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.2313C>T	p.His771His	synonymous	Exon 20 of 24	NP_001381131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	ENST00000684778.1	MANE Select	c.2397C>T	p.His799His	synonymous	Exon 20 of 24	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.2397C>T	p.His799His	synonymous	Exon 19 of 23	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.2397C>T	p.His799His	synonymous	Exon 20 of 24	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448030 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52278

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

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100468

Other (OTH) AF: 0.00 AC: 0 AN: 59956

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4511

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.3
DANN	Benign	0.63
PhyloP100		0.21

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: rs3812571; hg19: chr9-139275294;