9-136377647-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003086.4(SNAPC4):c.4180T>A(p.Ser1394Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1394L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNAPC4 NM_003086.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.08

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035134733).
• BP6: Variant 9-136377647-A-T is Benign according to our data. Variant chr9-136377647-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2237245.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC4	NM_003086.4	c.4180T>A	p.Ser1394Thr	missense_variant	22/24	ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.4180T>A	p.Ser1394Thr	missense_variant	22/24		NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.4180T>A	p.Ser1394Thr	missense_variant	21/23	1		P1
SNAPC4	ENST00000637388.2	c.4180T>A	p.Ser1394Thr	missense_variant	22/24	5		P1
SNAPC4	ENST00000689006.1	c.*3393T>A		3_prime_UTR_variant, NMD_transcript_variant	22/24

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441176 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 714466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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 Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.0010
Dann	Benign	0.51
DEOGEN2	Benign	0.00019	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	0.96	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.18		Gain of sheet (P = 0.0149);
MVP		0.12
ClinPred		0.046	T
GERP RS		-8.1
Varity_R		0.044
gMVP		0.075

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139272099;