15-40036464-G-C

Variant names:

• chr15-40036464-G-C
• rs8208
• NM_003134.6:c.280C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003134.6(SRP14):​c.280C>G​(p.Leu94Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L94L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRP14 NM_003134.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• Publications: 25 publications found

Genes affected

SRP14 (HGNC:11299): (signal recognition particle 14) Enables RNA binding activity. Involved in protein targeting to ER. Located in nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP14	NM_003134.6	c.280C>G	p.Leu94Val	missense_variant	Exon 5 of 5	ENST00000267884.11	NP_003125.3
SRP14	NM_001309434.1	c.136C>G	p.Leu46Val	missense_variant	Exon 6 of 6		NP_001296363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP14	ENST00000267884.11	c.280C>G	p.Leu94Val	missense_variant	Exon 5 of 5	1	NM_003134.6	ENSP00000267884.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 20250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Pathogenic	3.1	M;.;.
PhyloP100		4.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0050	D;D;D
Vest4		0.73
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.93
gMVP		0.42

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: rs8208; hg19: chr15-40328665;