1-225786829-A-G

Position:

• chr1-225786829-A-G

Variant summary

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

The NM_003133.6(SRP9):​c.142-2411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,247,838 control chromosomes in the GnomAD database, including 223,003 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 0.56 (24223 hom., cov: 28)
  • Exomes 𝑓: 0.60 (198780 hom.)
• Consequence: SRP9 NM_003133.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP9	NM_003133.6	c.142-2411A>G		intron_variant		ENST00000304786.12
SRP9	NM_001130440.2	c.142-33A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP9	ENST00000304786.12	c.142-2411A>G		intron_variant		1	NM_003133.6	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84201 AN: 150314 Hom.: 24203 Cov.: 28

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.552

GnomAD3 exomes AF: 0.628 AC: 73615 AN: 117218 Hom.: 23672 AF XY: 0.631 AC XY: 40617 AN XY: 64348

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.819

Gnomad SAS exome AF: 0.704

Gnomad FIN exome AF: 0.555

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.595

GnomAD4 exome AF: 0.597 AC: 655676 AN: 1097428 Hom.: 198780 Cov.: 27 AF XY: 0.602 AC XY: 324457 AN XY: 539216

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.686

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.808

Gnomad4 SAS exome AF: 0.701

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.560 AC: 84254 AN: 150410 Hom.: 24223 Cov.: 28 AF XY: 0.565 AC XY: 41441 AN XY: 73364

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.557

Alfa AF: 0.576 Hom.: 36766

Bravo AF: 0.557

Asia WGS AF: 0.749 AC: 2604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.56

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: rs4653433; hg19: chr1-225974531; COSMIC: COSV59158861;