rs572508224

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet
• acute myeloid leukemia

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

ENSG00000289393 (HGNC:58796):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 349129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 542 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	NM_006947.4	MANE Select	c.1640+6dupA		splice_region intron	N/A	NP_008878.3
	SRP72	NM_001267722.2		c.1457+6dupA		splice_region intron	N/A	NP_001254651.1	O76094-2
	SRP72	NR_151856.2		n.1659+6dupA		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	ENST00000642900.1	MANE Select	c.1640+6dupA		splice_region intron	N/A	ENSP00000495128.1	O76094-1
	SRP72	ENST00000510663.6	TSL:1	c.1457+6dupA		splice_region intron	N/A	ENSP00000424576.1	O76094-2
	SRP72	ENST00000925431.1		c.1634+6dupA		splice_region intron	N/A	ENSP00000595490.1

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

GnomAD2 exomes AF: 0.00320 AC: 800 AN: 249884 AF XY: 0.00358

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 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

African (AFR) AF: 0.000928 AC: 31 AN: 33406

American (AMR) AF: 0.00350 AC: 156 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00314 AC: 82 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00521 AC: 448 AN: 85932

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53354

Middle Eastern (MID) AF: 0.0137 AC: 79 AN: 5764

European-Non Finnish (NFE) AF: 0.00381 AC: 4229 AN: 1110980

Other (OTH) AF: 0.00365 AC: 220 AN: 60322

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

African (AFR) AF: 0.000866 AC: 36 AN: 41568

American (AMR) AF: 0.00902 AC: 138 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00437 AC: 297 AN: 68022

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Autosomal dominant aplasia and myelodysplasia (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=90/10	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs572508224;

hg19: chr4-57357739;