9-136380842-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003086.4(SNAPC4):​c.2397C>G​(p.His799Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,591,998 control chromosomes in the GnomAD database, including 150,875 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (13570 hom., cov: 33)
  • Exomes 𝑓: 0.43 (137305 hom.)
• Consequence: SNAPC4 NM_003086.4 missense
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2946129E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

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>G	p.His799Gln	missense	Exon 20 of 24	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.2397C>G	p.His799Gln	missense	Exon 20 of 24	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.2313C>G	p.His771Gln	missense	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>G	p.His799Gln	missense	Exon 20 of 24	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.2397C>G	p.His799Gln	missense	Exon 19 of 23	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.2397C>G	p.His799Gln	missense	Exon 20 of 24	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63698 AN: 151930 Hom.: 13544 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.429 AC: 106574 AN: 248460 AF XY: 0.420

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.297

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.443

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.432 AC: 622298 AN: 1439950 Hom.: 137305 Cov.: 29 AF XY: 0.428 AC XY: 307188 AN XY: 717466

African (AFR) AF: 0.366 AC: 12120 AN: 33128

American (AMR) AF: 0.562 AC: 25067 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 11593 AN: 25938

East Asian (EAS) AF: 0.317 AC: 12535 AN: 39588

South Asian (SAS) AF: 0.327 AC: 28096 AN: 85908

European-Finnish (FIN) AF: 0.421 AC: 22006 AN: 52236

Middle Eastern (MID) AF: 0.331 AC: 1901 AN: 5738

European-Non Finnish (NFE) AF: 0.443 AC: 483716 AN: 1093102

Other (OTH) AF: 0.423 AC: 25264 AN: 59718

GnomAD4 genome AF: 0.419 AC: 63782 AN: 152048 Hom.: 13570 Cov.: 33 AF XY: 0.417 AC XY: 31015 AN XY: 74304

African (AFR) AF: 0.375 AC: 15545 AN: 41472

American (AMR) AF: 0.517 AC: 7903 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1604 AN: 5168

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4383 AN: 10568

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29785 AN: 67950

Other (OTH) AF: 0.420 AC: 886 AN: 2110

Alfa AF: 0.438 Hom.: 4511

Bravo AF: 0.424

TwinsUK AF: 0.446 AC: 1654

ALSPAC AF: 0.447 AC: 1723

ESP6500AA AF: 0.364 AC: 1604

ESP6500EA AF: 0.443 AC: 3805

ExAC AF: 0.421 AC: 51061

Asia WGS AF: 0.395 AC: 1374 AN: 3478

EpiCase AF: 0.416

EpiControl AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.35
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.00013	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.5	N
PhyloP100		0.21
PrimateAI	Benign	0.44	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.088
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.29		Gain of helix (P = 0.0143)
ClinPred		0.0060	T
GERP RS		4.2
Varity_R		0.023
gMVP		0.25
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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; COSMIC: COSV53731483; COSMIC: COSV53731483;