rs3738037

chr1-225778101-C-Achr1-225778101-C-T

Variant summary

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

The NM_003133.6(SRP9):c.72+89C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,435,386 control chromosomes in the GnomAD database, including 17,988 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 0.22 (6207 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11781 hom.)
• Consequence: SRP9 NM_003133.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

Genes affected

SRP9 (HGNC:11304): (signal recognition particle 9) Predicted to enable RNA binding activity and signal recognition particle binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane. Predicted to be located in cytosol. Predicted to be part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP9	NM_003133.6	c.72+89C>A		intron_variant		ENST00000304786.12
SRP9	NM_001130440.2	c.72+89C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP9	ENST00000304786.12	c.72+89C>A		intron_variant		1	NM_003133.6	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33409 AN: 152050 Hom.: 6197 Cov.: 33

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.115 AC: 148206 AN: 1283218 Hom.: 11781 AF XY: 0.112 AC XY: 72279 AN XY: 642896

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0620

Gnomad4 FIN exome AF: 0.0921

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.220 AC: 33449 AN: 152168 Hom.: 6207 Cov.: 33 AF XY: 0.214 AC XY: 15934 AN XY: 74398

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.189

Alfa AF: 0.129 Hom.: 1854

Bravo AF: 0.239

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.9
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3738037; hg19: chr1-225965803; COSMIC: COSV59158820;