Genetic Variant NM_018556.4:c.*84G>A (chr20-1629555-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018556.4(SIRPG):c.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,250 control chromosomes in the GnomAD database, including 2,429 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 0.16 ( 2424 hom., cov: 31)

Exomes 𝑓: 0.22 ( 5 hom. )

Consequence

SIRPG
NM_018556.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.264

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	NM_018556.4 link	c.*84G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000303415.7	NP_061026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPG	ENST00000303415.7 link	c.*84G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_018556.4	ENSP00000305529.3

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24009

AN:

151972

Hom.:

2418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.219

AC:

AN:

160

Hom.:

Cov.:

AF XY:

0.206

AC XY:

AN XY:

102

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.217

AC:

AN:

106

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.158

AC:

24019

AN:

152090

Hom.:

2424

Cov.:

AF XY:

0.161

AC XY:

12004

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0413

AC:

1715

AN:

41506

American (AMR)

AF:

0.278

AC:

4243

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

577

AN:

3468

East Asian (EAS)

AF:

0.241

AC:

1245

AN:

5158

South Asian (SAS)

AF:

0.206

AC:

990

AN:

4808

European-Finnish (FIN)

AF:

0.186

AC:

1964

AN:

10584

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12675

AN:

67972

Other (OTH)

AF:

0.153

AC:

324

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

962

1925

2887

3850

4812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.181

Hom.:

3602

Bravo

AF:

0.160

Asia WGS

AF:

0.198

AC:

687

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.63

(source)

DANN

Benign

0.63

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

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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