rs754073133

Variant names:

• chr15-40036407-C-G
• rs754073133
• NM_003134.6:c.337G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-40036407-C-G
• chr15-40036407-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003134.6(SRP14):​c.337G>C​(p.Ala113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRP14 NM_003134.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09226003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003134.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP14	NM_003134.6	MANE Select	c.337G>C	p.Ala113Pro	missense	Exon 5 of 5	NP_003125.3
	SRP14	NM_001309434.1		c.193G>C	p.Ala65Pro	missense	Exon 6 of 6	NP_001296363.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP14	ENST00000267884.11	TSL:1 MANE Select	c.337G>C	p.Ala113Pro	missense	Exon 5 of 5	ENSP00000267884.6	P37108
	SRP14	ENST00000922619.1		c.403G>C	p.Ala135Pro	missense	Exon 5 of 5	ENSP00000592678.1
	SRP14	ENST00000922618.1		c.169G>C	p.Ala57Pro	missense	Exon 3 of 3	ENSP00000592677.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250866 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.0
DANN	Benign	0.47
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.83
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.036
Sift	Benign	0.054	T
Sift4G	Uncertain	0.029	D
Polyphen		0.0	B
Vest4		0.17
MutPred		0.36		Gain of glycosylation at A113 (P = 0.0045)
MVP		0.26
MPC		0.66
ClinPred		0.041	T
GERP RS		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.17

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: rs754073133; hg19: chr15-40328608;