Genetic Variant SRP72:c.-10C>T (chr4-56467626-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006947.4(SRP72):c.-10C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,541,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

SRP72
NM_006947.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.196

Publications

0 publications found

Variant links:

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

SRP72 links:

ENSG00000289393 (HGNC:58796):

ENSG00000289393 links:

LOC124900706 (HGNC:):

LOC124900706 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS2

High AC in GnomAdExome4 at 81 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRP72	NM_006947.4	MANE Select	c.-10C>T	5_prime_UTR	Exon 1 of 19	NP_008878.3
SRP72	NM_001267722.2		c.-10C>T	5_prime_UTR	Exon 1 of 17	NP_001254651.1	O76094-2
SRP72	NR_151856.2		n.10C>T	non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRP72	ENST00000642900.1	MANE Select	c.-10C>T	5_prime_UTR	Exon 1 of 19	ENSP00000495128.1	O76094-1
SRP72	ENST00000510663.6	TSL:1	c.-10C>T	5_prime_UTR	Exon 1 of 17	ENSP00000424576.1	O76094-2
SRP72	ENST00000925431.1		c.-10C>T	5_prime_UTR	Exon 1 of 19	ENSP00000595490.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000326

AC:

AN:

183944

AF XY:

0.0000488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000469

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000579

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000583

AC:

AN:

1389468

Hom.:

Cov.:

AF XY:

0.0000640

AC XY:

AN XY:

687968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29196

American (AMR)

AF:

0.0000317

AC:

AN:

31592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23502

East Asian (EAS)

AF:

0.00

AC:

AN:

34434

South Asian (SAS)

AF:

0.0000128

AC:

AN:

77924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.0000649

AC:

AN:

1078368

Other (OTH)

AF:

0.000158

AC:

AN:

57064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant aplasia and myelodysplasia (1)

SRP72-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.20

PromoterAI

0.15

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over