Genetic Variant NM_018556.4:c.1140C>T (chr20-1630248-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_018556.4(SIRPG):c.1140C>T(p.Tyr380Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,569,130 control chromosomes in the GnomAD database, including 59,925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5274 hom., cov: 31)

Exomes 𝑓: 0.26 ( 54651 hom. )

Consequence

SIRPG
NM_018556.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70

Publications

17 publications found

Variant links:

Genes affected

SIRPG (HGNC:15757): (signal regulatory protein gamma) The protein encoded by this gene is a member of the signal-regulatory protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SIRPG Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

SIRPG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP7

Synonymous conserved (PhyloP=-1.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	NM_018556.4 link	c.1140C>T	p.Tyr380Tyr	synonymous_variant	Exon 5 of 6	ENST00000303415.7	NP_061026.2	Q9P1W8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPG	ENST00000303415.7 link	c.1140C>T	p.Tyr380Tyr	synonymous_variant	Exon 5 of 6	1	NM_018556.4	ENSP00000305529.3		Q9P1W8-1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36364

AN:

151846

Hom.:

5279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.279

GnomAD2 exomes

AF:

0.302

AC:

57237

AN:

189316

AF XY:

0.313

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.263

AC:

372430

AN:

1417164

Hom.:

54651

Cov.:

AF XY:

0.270

AC XY:

189025

AN XY:

701004

show subpopulations

African (AFR)

AF:

0.112

AC:

3675

AN:

32812

American (AMR)

AF:

0.289

AC:

11159

AN:

38648

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

8798

AN:

25346

East Asian (EAS)

AF:

0.586

AC:

22157

AN:

37818

South Asian (SAS)

AF:

0.456

AC:

36800

AN:

80692

European-Finnish (FIN)

AF:

0.266

AC:

13402

AN:

50444

Middle Eastern (MID)

AF:

0.387

AC:

2077

AN:

5370

European-Non Finnish (NFE)

AF:

0.237

AC:

257683

AN:

1087296

Other (OTH)

AF:

0.284

AC:

16679

AN:

58738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

12843

25685

38528

51370

64213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8932

17864

26796

35728

44660

<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:

0.239

AC:

36369

AN:

151966

Hom.:

5274

Cov.:

AF XY:

0.246

AC XY:

18306

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.119

AC:

4953

AN:

41460

American (AMR)

AF:

0.275

AC:

4197

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1268

AN:

3472

East Asian (EAS)

AF:

0.606

AC:

3119

AN:

5148

South Asian (SAS)

AF:

0.477

AC:

2292

AN:

4800

European-Finnish (FIN)

AF:

0.256

AC:

2704

AN:

10566

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16975

AN:

67926

Other (OTH)

AF:

0.281

AC:

593

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1353

2705

4058

5410

6763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.252

Hom.:

18085

Bravo

AF:

0.232

Asia WGS

AF:

0.519

AC:

1804

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.71

(source)

DANN

Benign

0.50

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over