chr19-40763171-T-C

Position:

• chr19-40763171-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004596.5(SNRPA):​c.600+97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 952,128 control chromosomes in the GnomAD database, including 54,310 homozygotes. 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: 𝑓 0.27 (7111 hom., cov: 32)
  • Exomes 𝑓: 0.34 (47199 hom.)
• Consequence: SNRPA NM_004596.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

Genes affected

SNRPA (HGNC:11151): (small nuclear ribonucleoprotein polypeptide A) The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

SNRPA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRPA	NM_004596.5	c.600+97T>C		intron_variant		ENST00000243563.8	NP_004587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRPA	ENST00000243563.8	c.600+97T>C		intron_variant		1	NM_004596.5	ENSP00000243563.2
SNRPA	ENST00000601393.1	c.537+97T>C		intron_variant		3		ENSP00000472355.1
SNRPA	ENST00000601545.5	c.450+97T>C		intron_variant		5		ENSP00000470534.1
SNRPA	ENST00000598923.1	n.832T>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41465 AN: 151990 Hom.: 7105 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.341 AC: 272758 AN: 800020 Hom.: 47199 Cov.: 10 AF XY: 0.340 AC XY: 137284 AN XY: 403412

Gnomad4 AFR exome AF: 0.0590

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.273 AC: 41480 AN: 152108 Hom.: 7111 Cov.: 32 AF XY: 0.277 AC XY: 20575 AN XY: 74350

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.292

Alfa AF: 0.325 Hom.: 9965

Bravo AF: 0.270

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2305797; hg19: chr19-41269076; COSMIC: COSV54683297; COSMIC: COSV54683297;