chr5-112862289-A-T

Variant names:

• chr5-112862289-A-T
• rs431287
• NM_003135.3:c.42-219A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003135.3(SRP19):​c.42-219A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 588,038 control chromosomes in the GnomAD database, including 136,161 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 0.64 (31788 hom., cov: 31)
  • Exomes 𝑓: 0.69 (104373 hom.)
• Consequence: SRP19 NM_003135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 5 publications found

Genes affected

SRP19 (HGNC:11300): (signal recognition particle 19) Enables 7S RNA binding activity. Contributes to ribosome binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition. Located in nucleolus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP19	NM_003135.3	MANE Select	c.42-219A>T		intron	N/A	NP_003126.1
	SRP19	NM_001204194.2		c.42-219A>T		intron	N/A	NP_001191123.1
	SRP19	NM_001204193.2		c.42-219A>T		intron	N/A	NP_001191122.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP19	ENST00000505459.6	TSL:1 MANE Select	c.42-219A>T		intron	N/A	ENSP00000424870.1
	SRP19	ENST00000282999.7	TSL:1	c.42-219A>T		intron	N/A	ENSP00000282999.3
	ENSG00000258864	ENST00000520401.1	TSL:3	n.254-219A>T		intron	N/A	ENSP00000454861.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97745 AN: 151724 Hom.: 31780 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.689 AC: 300595 AN: 436196 Hom.: 104373 AF XY: 0.692 AC XY: 162352 AN XY: 234526

African (AFR) AF: 0.556 AC: 6648 AN: 11964

American (AMR) AF: 0.740 AC: 13705 AN: 18514

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 8727 AN: 13688

East Asian (EAS) AF: 0.848 AC: 24339 AN: 28702

South Asian (SAS) AF: 0.742 AC: 34238 AN: 46154

European-Finnish (FIN) AF: 0.673 AC: 18436 AN: 27380

Middle Eastern (MID) AF: 0.668 AC: 1284 AN: 1922

European-Non Finnish (NFE) AF: 0.671 AC: 176326 AN: 262920

Other (OTH) AF: 0.677 AC: 16892 AN: 24952

GnomAD4 genome AF: 0.644 AC: 97803 AN: 151842 Hom.: 31788 Cov.: 31 AF XY: 0.647 AC XY: 47997 AN XY: 74192

African (AFR) AF: 0.552 AC: 22879 AN: 41416

American (AMR) AF: 0.701 AC: 10699 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2131 AN: 3472

East Asian (EAS) AF: 0.825 AC: 4250 AN: 5152

South Asian (SAS) AF: 0.757 AC: 3630 AN: 4796

European-Finnish (FIN) AF: 0.631 AC: 6638 AN: 10526

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45386 AN: 67912

Other (OTH) AF: 0.652 AC: 1373 AN: 2106

Alfa AF: 0.544 Hom.: 1529

Bravo AF: 0.646

Asia WGS AF: 0.771 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.4
DANN	Benign	0.38
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs431287; hg19: chr5-112197986;