rs17290456

Variant names:

• chr5-112865274-T-C
• rs17290456
• NM_003135.3:c.301+542T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.89).
• 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 rank	MANE	Protein	UniProt
SRP19	NM_003135.3	c.301+542T>C		intron_variant	Intron 4 of 4	ENST00000505459.6	NP_003126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP19	ENST00000505459.6	c.301+542T>C		intron_variant	Intron 4 of 4	1	NM_003135.3	ENSP00000424870.1
ENSG00000258864	ENST00000520401.1	n.*231+542T>C		intron_variant	Intron 7 of 7	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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0385 AC: 4 AN: 104

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.0123 AC: 510 AN: 41558

American (AMR) AF: 0.0478 AC: 731 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00934 AC: 45 AN: 4820

European-Finnish (FIN) AF: 0.0129 AC: 137 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0669 AC: 4548 AN: 68030

Other (OTH) AF: 0.0493 AC: 104 AN: 2108

Alfa AF: 0.0565 Hom.: 202

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
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism

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: rs17290456; hg19: chr5-112200971;