chr4-56483196-G-A

Position:

• chr4-56483196-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006947.4(SRP72):​c.883G>A​(p.Glu295Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRP72 NM_006947.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.88

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP72	NM_006947.4	c.883G>A	p.Glu295Lys	missense_variant	9/19	ENST00000642900.1	NP_008878.3
SRP72	NM_001267722.2	c.700G>A	p.Glu234Lys	missense_variant	7/17		NP_001254651.1
SRP72	XM_024454192.2	c.883G>A	p.Glu295Lys	missense_variant	9/17		XP_024309960.1
SRP72	NR_151856.2	n.902G>A		non_coding_transcript_exon_variant	9/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.883G>A	p.Glu295Lys	missense_variant	9/19		NM_006947.4	ENSP00000495128.1
SRP72	ENST00000510663.6	c.700G>A	p.Glu234Lys	missense_variant	7/17	1		ENSP00000424576.1
SRP72	ENST00000505314.2	c.724-1540G>A		intron_variant		3		ENSP00000425190.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 27, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;.
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.8	D;D;.
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	D;T;.
Sift4G	Uncertain	0.019	D;D;.
Polyphen		0.40	B;.;B
Vest4		0.94
MutPred		0.42		Gain of MoRF binding (P = 0.0027);.;Gain of MoRF binding (P = 0.0027);
MVP		0.85
MPC		0.31
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.46

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: rs797046010; hg19: chr4-57349362;