rs145347209

chr4-56500555-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006947.4(SRP72):c.1698T>C(p.Tyr566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,613,342 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (1 hom.)
• Consequence: SRP72 NM_006947.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.313

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 4-56500555-T-C is Benign according to our data. Variant chr4-56500555-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 349132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.313 with no splicing effect.
• BS2: High AC in GnomAd at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP72	NM_006947.4	c.1698T>C	p.Tyr566=	synonymous_variant	18/19	ENST00000642900.1
SRP72	NM_001267722.2	c.1515T>C	p.Tyr505=	synonymous_variant	16/17
SRP72	NR_151856.2	n.1831T>C		non_coding_transcript_exon_variant	19/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP72	ENST00000642900.1	c.1698T>C	p.Tyr566=	synonymous_variant	18/19		NM_006947.4	P1
SRP72	ENST00000510663.6	c.1515T>C	p.Tyr505=	synonymous_variant	16/17	1
SRP72	ENST00000507126.3	n.105T>C		non_coding_transcript_exon_variant	1/2	1
SRP72	ENST00000646222.1	n.144T>C		non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000467 AC: 117 AN: 250578 Hom.: 1 AF XY: 0.000531 AC XY: 72 AN XY: 135492

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000818

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000671

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000558 AC: 816 AN: 1461060 Hom.: 1 Cov.: 30 AF XY: 0.000590 AC XY: 429 AN XY: 726848

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000586

Gnomad4 OTH exome AF: 0.000630

GnomAD4 genome AF: 0.000401 AC: 61 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74462

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.000374

EpiCase AF: 0.00104

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	SRP72: BP4 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 06, 2024	- -

SRP72-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 27, 2016

- -

Autosomal dominant aplasia and myelodysplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	5.6
Dann	Benign	0.70

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: rs145347209; hg19: chr4-57366721;