rs3738037

Variant names:

• chr1-225778101-C-A
• rs3738037
• NM_003133.6:c.72+89C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-225778101-C-A
• chr1-225778101-C-G
• chr1-225778101-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SRP9	NM_003133.6	c.72+89C>A		intron_variant	Intron 1 of 2	ENST00000304786.12	NP_003124.1
SRP9	NM_001130440.2	c.72+89C>A		intron_variant	Intron 1 of 3		NP_001123912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP9	ENST00000304786.12	c.72+89C>A		intron_variant	Intron 1 of 2	1	NM_003133.6	ENSP00000305230.7

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

African (AFR) AF: 0.532 AC: 15571 AN: 29254

American (AMR) AF: 0.135 AC: 4973 AN: 36832

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 1815 AN: 23702

East Asian (EAS) AF: 0.104 AC: 3843 AN: 36902

South Asian (SAS) AF: 0.0620 AC: 4893 AN: 78886

European-Finnish (FIN) AF: 0.0921 AC: 4699 AN: 51028

Middle Eastern (MID) AF: 0.120 AC: 645 AN: 5390

European-Non Finnish (NFE) AF: 0.109 AC: 104962 AN: 967000

Other (OTH) AF: 0.125 AC: 6805 AN: 54224

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

African (AFR) AF: 0.511 AC: 21202 AN: 41480

American (AMR) AF: 0.159 AC: 2433 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.0724 AC: 375 AN: 5178

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4826

European-Finnish (FIN) AF: 0.0886 AC: 940 AN: 10610

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7375 AN: 67986

Other (OTH) AF: 0.189 AC: 400 AN: 2114

Alfa AF: 0.153 Hom.: 7803

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
PhyloP100		-0.57
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3738037; hg19: chr1-225965803; COSMIC: COSV59158820;