rs7535

Positions:

• chr15-40036374-G-A
• chr15-40036374-G-C
• chr15-40036374-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003134.6(SRP14):​c.370C>T​(p.Pro124Ser) 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. 14/21 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. P124A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: SRP14 NM_003134.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060103238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP14	NM_003134.6	c.370C>T	p.Pro124Ser	missense_variant	5/5	ENST00000267884.11
SRP14	NM_001309434.1	c.226C>T	p.Pro76Ser	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP14	ENST00000267884.11	c.370C>T	p.Pro124Ser	missense_variant	5/5	1	NM_003134.6	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.1
DANN	Benign	0.87
DEOGEN2	Benign	0.038	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.29	T;.;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.21	N;D;D
REVEL	Benign	0.027
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.093
MutPred		0.14		Loss of loop (P = 0.0075);.;.;
MVP		0.28
MPC		0.51
ClinPred		0.057	T
GERP RS		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.097
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

Publications

LitVar

Other links and lift over

dbSNP: rs7535; hg19: chr15-40328575;