9-136377887-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003086.4(SNAPC4):c.3940C>T(p.Leu1314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0009 in 1,611,472 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00090 (2 hom.)
• Consequence: SNAPC4 NM_003086.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.88

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-136377887-G-A is Benign according to our data. Variant chr9-136377887-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659732.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-136377887-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC4	NM_003086.4	c.3940C>T	p.Leu1314=	synonymous_variant	22/24	ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.3940C>T	p.Leu1314=	synonymous_variant	22/24		NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.3940C>T	p.Leu1314=	synonymous_variant	21/23	1		P1
SNAPC4	ENST00000637388.2	c.3940C>T	p.Leu1314=	synonymous_variant	22/24	5		P1
SNAPC4	ENST00000689006.1	c.*3153C>T		3_prime_UTR_variant, NMD_transcript_variant	22/24

Frequencies

GnomAD3 genomes AF: 0.000900 AC: 137 AN: 152190 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000630 AC: 151 AN: 239810 Hom.: 1 AF XY: 0.000638 AC XY: 84 AN XY: 131578

Gnomad AFR exome AF: 0.0000673

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000338

Gnomad NFE exome AF: 0.00124

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000901 AC: 1314 AN: 1459164 Hom.: 2 Cov.: 41 AF XY: 0.000887 AC XY: 644 AN XY: 725886

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000392

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.000899 AC: 137 AN: 152308 Hom.: 0 Cov.: 34 AF XY: 0.000873 AC XY: 65 AN XY: 74478

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00181 Hom.: 1

Bravo AF: 0.000691

EpiCase AF: 0.00120

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

SNAPC4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.54
Dann	Benign	0.57

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: rs144874677; hg19: chr9-139272339;