5-112865274-T-C

Position:

• chr5-112865274-T-C

Variant summary

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

The NM_003135.3(SRP19):​c.301+542T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,414 control chromosomes in the GnomAD database, including 218 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 0.042 (218 hom., cov: 32)
  • Exomes 𝑓: 0.040 (0 hom.)
• Consequence: SRP19 NM_003135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP19	NM_003135.3	c.301+542T>C		intron_variant		ENST00000505459.6	NP_003126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP19	ENST00000505459.6	c.301+542T>C		intron_variant		1	NM_003135.3	ENSP00000424870.1
ENSG00000258864	ENST00000520401.1	n.*231+542T>C		intron_variant		3		ENSP00000454861.1

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6434 AN: 152170 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0669

Gnomad OTH AF: 0.0499

GnomAD4 exome AF: 0.0403 AC: 5 AN: 124 Hom.: 0 AF XY: 0.0323 AC XY: 2 AN XY: 62

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0422 AC: 6434 AN: 152290 Hom.: 218 Cov.: 32 AF XY: 0.0388 AC XY: 2887 AN XY: 74462

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0669

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0585 Hom.: 113

Bravo AF: 0.0448

Asia WGS AF: 0.00924 AC: 33 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.57

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: rs17290456; hg19: chr5-112200971;