rs572508224

Variant names:

• chr4-56491573-T-TA
• rs572508224
• NM_006947.4:c.1640+6dupA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_006947.4(SRP72):​c.1640+6dupA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,612,326 control chromosomes in the GnomAD database, including 29 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (23 hom.)
• Consequence: SRP72 NM_006947.4 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.187

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 4-56491573-T-TA is Benign according to our data. Variant chr4-56491573-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 349129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 542 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4	c.1640+6dupA		splice_region_variant, intron_variant	Intron 16 of 18	ENST00000642900.1	NP_008878.3
SRP72	NM_001267722.2	c.1457+6dupA		splice_region_variant, intron_variant	Intron 14 of 16		NP_001254651.1
SRP72	XM_024454192.2	c.1640+6dupA		splice_region_variant, intron_variant	Intron 16 of 16		XP_024309960.1
SRP72	NR_151856.2	n.1659+6dupA		splice_region_variant, intron_variant	Intron 16 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.1640+6dupA		splice_region_variant, intron_variant	Intron 16 of 18		NM_006947.4	ENSP00000495128.1
SRP72	ENST00000510663.6	c.1457+6dupA		splice_region_variant, intron_variant	Intron 14 of 16	1		ENSP00000424576.1
SRP72	ENST00000646579.1	n.657dupA		non_coding_transcript_exon_variant	Exon 6 of 6
SRP72	ENST00000647432.1	n.742+6dupA		splice_region_variant, intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 543 AN: 152176 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00437

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00320 AC: 800 AN: 249884 Hom.: 9 AF XY: 0.00358 AC XY: 484 AN XY: 135060

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00290

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00514

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.00412

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00362 AC: 5282 AN: 1460032 Hom.: 23 Cov.: 30 AF XY: 0.00376 AC XY: 2731 AN XY: 726226

Gnomad4 AFR exome AF: 0.000928

Gnomad4 AMR exome AF: 0.00350

Gnomad4 ASJ exome AF: 0.00314

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00521

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00365

GnomAD4 genome AF: 0.00356 AC: 542 AN: 152294 Hom.: 6 Cov.: 32 AF XY: 0.00380 AC XY: 283 AN XY: 74468

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00437

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00350 Hom.: 1

Bravo AF: 0.00382

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00460

EpiControl AF: 0.00569

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 11, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SRP72: BP4, BS2 -

Autosomal dominant aplasia and myelodysplasia Benign:2

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 28, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs572508224; hg19: chr4-57357739;