rs572508224

chr4-56491573-T-TA

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+6dup variant causes a splice donor 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. 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_donor_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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 GnomAd at 543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP72	NM_006947.4	c.1640+6dup		splice_donor_region_variant, intron_variant		ENST00000642900.1
SRP72	NM_001267722.2	c.1457+6dup		splice_donor_region_variant, intron_variant
SRP72	XM_024454192.2	c.1640+6dup		splice_donor_region_variant, intron_variant
SRP72	NR_151856.2	n.1659+6dup		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP72	ENST00000642900.1	c.1640+6dup		splice_donor_region_variant, intron_variant			NM_006947.4	P1
SRP72	ENST00000510663.6	c.1457+6dup		splice_donor_region_variant, intron_variant		1
SRP72	ENST00000646579.1	n.657dup		non_coding_transcript_exon_variant	6/6
SRP72	ENST00000647432.1	n.742+6dup		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2023	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 28, 2016

- -

Autosomal dominant aplasia and myelodysplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;