5-112867437-T-C

Position:

• chr5-112867437-T-C

Variant summary

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

The ENST00000505459.6(SRP19):​c.335T>C​(p.Ile112Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRP19 ENST00000505459.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24

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]

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, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP19	NM_003135.3	c.335T>C	p.Ile112Thr	missense_variant	5/5	ENST00000505459.6	NP_003126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP19	ENST00000505459.6	c.335T>C	p.Ile112Thr	missense_variant	5/5	1	NM_003135.3	ENSP00000424870	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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

May 20, 2024

The c.335T>C (p.I112T) alteration is located in exon 5 (coding exon 5) of the SRP19 gene. This alteration results from a T to C substitution at nucleotide position 335, causing the isoleucine (I) at amino acid position 112 to be replaced by a threonine (T). 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	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.9	M;.
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Pathogenic	-4.6	D;.
REVEL	Uncertain	0.59
Sift	Benign	0.056	T;.
Sift4G	Uncertain	0.059	T;T
Polyphen		0.16	B;.
Vest4		0.88
MutPred		0.77		Gain of disorder (P = 0.0141);.;
MVP		0.81
MPC		0.59
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr5-112203134;