rs192401229

Positions:

• chr4-56491517-T-A
• chr4-56491517-T-C

Variant summary

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

The NM_006947.4(SRP72):​c.1589T>A​(p.Ile530Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRP72 NM_006947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.62

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.1589T>A	p.Ile530Asn	missense_variant	16/19	ENST00000642900.1	NP_008878.3
SRP72	NM_001267722.2	c.1406T>A	p.Ile469Asn	missense_variant	14/17		NP_001254651.1
SRP72	XM_024454192.2	c.1589T>A	p.Ile530Asn	missense_variant	16/17		XP_024309960.1
SRP72	NR_151856.2	n.1608T>A		non_coding_transcript_exon_variant	16/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.1589T>A	p.Ile530Asn	missense_variant	16/19		NM_006947.4	ENSP00000495128	P1
SRP72	ENST00000510663.6	c.1406T>A	p.Ile469Asn	missense_variant	14/17	1		ENSP00000424576
SRP72	ENST00000646579.1	n.600T>A		non_coding_transcript_exon_variant	6/6
SRP72	ENST00000647432.1	n.691T>A		non_coding_transcript_exon_variant	4/5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251322 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D;.
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.9	L;.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Uncertain	0.51
Sift	Benign	0.096	T;D;.
Sift4G	Benign	0.17	T;D;.
Polyphen		0.96	D;.;D
Vest4		0.53
MutPred		0.44		Loss of helix (P = 0.0237);.;Loss of helix (P = 0.0237);
MVP		0.90
MPC		0.64
ClinPred		0.96	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.41

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: rs192401229; hg19: chr4-57357683;