rs529395062

Variant names:

• chr4-56467644-C-G
• rs529395062
• NM_006947.4:c.9C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-56467644-C-G
• chr4-56467644-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006947.4(SRP72):​c.9C>G​(p.Ser3Arg) 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. 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. S3G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SRP72 NM_006947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

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]

SRP72 Gene-Disease associations (from GenCC):

• autosomal dominant aplasia and myelodysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• acute myeloid leukemia

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

ENSG00000289393 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28095472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4	c.9C>G	p.Ser3Arg	missense_variant	Exon 1 of 19	ENST00000642900.1	NP_008878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.9C>G	p.Ser3Arg	missense_variant	Exon 1 of 19		NM_006947.4	ENSP00000495128.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;.;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.81	T;T;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.69	N;N;N;.
PhyloP100		1.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N;N;.;.
REVEL	Uncertain	0.42
Sift	Benign	0.17	T;T;.;.
Sift4G	Benign	0.42	T;T;.;T
Polyphen		0.65	P;.;P;.
Vest4		0.39
MutPred		0.28		Loss of glycosylation at S3 (P = 0.0072);Loss of glycosylation at S3 (P = 0.0072);Loss of glycosylation at S3 (P = 0.0072);Loss of glycosylation at S3 (P = 0.0072);
MVP		0.76
MPC		0.26
ClinPred		0.64	D
GERP RS		3.0
PromoterAI		-0.34	Neutral
Varity_R		0.11
gMVP		0.31
Mutation Taster		=87/13	polymorphism

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: rs529395062; hg19: chr4-57333810;