5-112862510-T-C

Position:

• chr5-112862510-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003135.3(SRP19):​c.44T>C​(p.Phe15Ser) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRP19 NM_003135.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP19	NM_003135.3	c.44T>C	p.Phe15Ser	missense_variant, splice_region_variant	2/5	ENST00000505459.6	NP_003126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP19	ENST00000505459.6	c.44T>C	p.Phe15Ser	missense_variant, splice_region_variant	2/5	1	NM_003135.3	ENSP00000424870.1
ENSG00000258864	ENST00000520401.1	n.256T>C		splice_region_variant, non_coding_transcript_exon_variant	5/8	3		ENSP00000454861.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.44T>C (p.F15S) alteration is located in exon 2 (coding exon 2) of the SRP19 gene. This alteration results from a T to C substitution at nucleotide position 44, causing the phenylalanine (F) at amino acid position 15 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	.;T;.;.;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.1	.;M;M;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.3	.;D;D;N;.;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	.;D;D;T;.;.
Sift4G	Uncertain	0.016	.;D;D;.;D;D
Polyphen		1.0	.;D;.;.;.;.
Vest4		0.91, 0.89, 0.95, 0.86
MutPred		0.72		Gain of disorder (P = 0.0035);Gain of disorder (P = 0.0035);Gain of disorder (P = 0.0035);Gain of disorder (P = 0.0035);Gain of disorder (P = 0.0035);Gain of disorder (P = 0.0035);
MVP		0.76
MPC		0.86
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.97
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112198207;