NM_003135.3:c.42-219A>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003135.3(SRP19):​c.42-219A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 436,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000069 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>C		intron	N/A	NP_003126.1
	SRP19	NM_001204194.2		c.42-219A>C		intron	N/A	NP_001191123.1
	SRP19	NM_001204193.2		c.42-219A>C		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>C		intron	N/A	ENSP00000424870.1
	SRP19	ENST00000282999.7	TSL:1	c.42-219A>C		intron	N/A	ENSP00000282999.3
	ENSG00000258864	ENST00000520401.1	TSL:3	n.254-219A>C		intron	N/A	ENSP00000454861.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000687 AC: 3 AN: 436806 Hom.: 0 AF XY: 0.00000426 AC XY: 1 AN XY: 234870

African (AFR) AF: 0.00 AC: 0 AN: 11984

American (AMR) AF: 0.00 AC: 0 AN: 18540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13714

East Asian (EAS) AF: 0.00 AC: 0 AN: 28728

South Asian (SAS) AF: 0.00 AC: 0 AN: 46180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1926

European-Non Finnish (NFE) AF: 0.0000114 AC: 3 AN: 263332

Other (OTH) AF: 0.00 AC: 0 AN: 24976

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.070
PhyloP100		-1.4

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;