20-1629905-T-C

Variant names:

• chr20-1629905-T-C
• rs2281808
• NM_018556.4:c.*3-269A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000303415.7(SIRPG):​c.*3-269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,976 control chromosomes in the GnomAD database, including 38,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (38698 hom., cov: 30)
• Consequence: SIRPG ENST00000303415.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.509
• Publications: 80 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 20-1629905-T-C is Benign according to our data. Variant chr20-1629905-T-C is described in ClinVar as Benign. ClinVar VariationId is 1276615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000303415.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPG	NM_018556.4	MANE Select	c.*3-269A>G		intron	N/A	NP_061026.2
	SIRPG	NM_001039508.2		c.*3-269A>G		intron	N/A	NP_001034597.1
	SIRPG	NM_080816.3		c.*3-269A>G		intron	N/A	NP_543006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPG	ENST00000303415.7	TSL:1 MANE Select	c.*3-269A>G		intron	N/A	ENSP00000305529.3
	SIRPG	ENST00000381580.5	TSL:1	c.*3-269A>G		intron	N/A	ENSP00000370992.1
	SIRPG	ENST00000344103.8	TSL:1	c.*3-269A>G		intron	N/A	ENSP00000342759.4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107944 AN: 151858 Hom.: 38671 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.717

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.711 AC: 108028 AN: 151976 Hom.: 38698 Cov.: 30 AF XY: 0.718 AC XY: 53317 AN XY: 74286

African (AFR) AF: 0.765 AC: 31710 AN: 41450

American (AMR) AF: 0.750 AC: 11464 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2557 AN: 3470

East Asian (EAS) AF: 0.837 AC: 4306 AN: 5146

South Asian (SAS) AF: 0.852 AC: 4100 AN: 4812

European-Finnish (FIN) AF: 0.698 AC: 7372 AN: 10564

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44279 AN: 67940

Other (OTH) AF: 0.719 AC: 1520 AN: 2114

Alfa AF: 0.675 Hom.: 116280

Bravo AF: 0.712

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.82
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2281808; hg19: chr20-1610551;