rs777589749

Variant names:

• chr4-56467653-C-A
• rs777589749
• NM_006947.4:c.18C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-56467653-C-A
• chr4-56467653-C-G
• chr4-56467653-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006947.4(SRP72):​c.18C>A​(p.Ser6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SRP72 NM_006947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 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, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• acute myeloid leukemia

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

ENSG00000289393 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07736239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP72	NM_006947.4	c.18C>A	p.Ser6Arg	missense_variant	Exon 1 of 19	ENST00000642900.1	NP_008878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP72	ENST00000642900.1	c.18C>A	p.Ser6Arg	missense_variant	Exon 1 of 19		NM_006947.4	ENSP00000495128.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399356 Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1 AN XY: 694704

African (AFR) AF: 0.00 AC: 0 AN: 29592

American (AMR) AF: 0.00 AC: 0 AN: 35234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24186

East Asian (EAS) AF: 0.00 AC: 0 AN: 34008

South Asian (SAS) AF: 0.00 AC: 0 AN: 80204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081606

Other (OTH) AF: 0.00 AC: 0 AN: 57412

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.029	T;.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.22	T;T;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.90	L;L;L;.
PhyloP100		-1.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;N;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.019	D;D;.;.
Sift4G	Benign	0.094	T;T;.;D
Polyphen		0.31	B;.;B;.
Vest4		0.12
MutPred		0.36		Loss of glycosylation at S6 (P = 7e-04);Loss of glycosylation at S6 (P = 7e-04);Loss of glycosylation at S6 (P = 7e-04);Loss of glycosylation at S6 (P = 7e-04);
MVP		0.43
MPC		0.27
ClinPred		0.28	T
GERP RS		-2.6
PromoterAI		-0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.21
gMVP		0.13
Mutation Taster		=85/15	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: rs777589749; hg19: chr4-57333819;