4-56467693-C-G

Position:

• chr4-56467693-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006947.4(SRP72):​c.58C>G​(p.Arg20Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R20W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SRP72 NM_006947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

Genes affected

SRP72 (HGNC:11303): (signal recognition particle 72) This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP72	NM_006947.4	c.58C>G	p.Arg20Gly	missense_variant	1/19	ENST00000642900.1	NP_008878.3
SRP72	NM_001267722.2	c.58C>G	p.Arg20Gly	missense_variant	1/17		NP_001254651.1
SRP72	XM_024454192.2	c.58C>G	p.Arg20Gly	missense_variant	1/17		XP_024309960.1
SRP72	NR_151856.2	n.77C>G		non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.58C>G	p.Arg20Gly	missense_variant	1/19		NM_006947.4	ENSP00000495128.1
SRP72	ENST00000510663.6	c.58C>G	p.Arg20Gly	missense_variant	1/17	1		ENSP00000424576.1
SRP72	ENST00000504757.2	c.58C>G	p.Arg20Gly	missense_variant	1/5	2		ENSP00000473576.1
SRP72	ENST00000505314.2	c.-45C>G		upstream_gene_variant		3		ENSP00000425190.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.93	D;D;.;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M;M;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.2	D;D;.;.
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D;.;.
Sift4G	Uncertain	0.0060	D;D;.;D
Polyphen		0.96	D;.;D;.
Vest4		0.64
MutPred		0.52		Loss of stability (P = 0.0438);Loss of stability (P = 0.0438);Loss of stability (P = 0.0438);Loss of stability (P = 0.0438);
MVP		0.56
MPC		0.92
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs111673705; hg19: chr4-57333859;