rs148068843

Variant names:

• chr4-56501849-A-G
• rs148068843
• NM_006947.4:c.2004A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006947.4(SRP72):​c.2004A>G​(p.Lys668Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,112 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: SRP72 NM_006947.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.55
• Publications: 2 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• acute myeloid leukemia

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

ENSG00000289393 (HGNC:58796):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.164).
• BP6: Variant 4-56501849-A-G is Benign according to our data. Variant chr4-56501849-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 349135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.55 with no splicing effect.
• BS2: High AC in GnomAd4 at 159 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.2004A>G	p.Lys668Lys	synonymous	Exon 19 of 19	NP_008878.3
	SRP72	NM_001267722.2		c.1821A>G	p.Lys607Lys	synonymous	Exon 17 of 17	NP_001254651.1	O76094-2
	SRP72	NR_151856.2		n.2137A>G		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	ENST00000642900.1	MANE Select	c.2004A>G	p.Lys668Lys	synonymous	Exon 19 of 19	ENSP00000495128.1	O76094-1
	SRP72	ENST00000510663.6	TSL:1	c.1821A>G	p.Lys607Lys	synonymous	Exon 17 of 17	ENSP00000424576.1	O76094-2
	SRP72	ENST00000507126.3	TSL:1	n.411A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 159 AN: 152188 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000743 AC: 186 AN: 250216 AF XY: 0.000781

Gnomad AFR exome AF: 0.0000645

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00123 AC: 1802 AN: 1461806 Hom.: 1 Cov.: 31 AF XY: 0.00122 AC XY: 884 AN XY: 727202

African (AFR) AF: 0.000269 AC: 9 AN: 33478

American (AMR) AF: 0.00105 AC: 47 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00151 AC: 1680 AN: 1111964

Other (OTH) AF: 0.00103 AC: 62 AN: 60386

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152306 Hom.: 2 Cov.: 32 AF XY: 0.00114 AC XY: 85 AN XY: 74476

African (AFR) AF: 0.000265 AC: 11 AN: 41568

American (AMR) AF: 0.00281 AC: 43 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 68026

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00114 Hom.: 2

Bravo AF: 0.00126

EpiCase AF: 0.00104

EpiControl AF: 0.00148

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.6
DANN	Benign	0.89
PhyloP100		2.6
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs148068843; hg19: chr4-57368015; COSMIC: COSV100714418; COSMIC: COSV100714418;