rs238224

Variant names:

• chr17-4960115-A-G
• rs238224
• NM_004890.3:c.328-4T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-4960115-A-G
• chr17-4960115-A-C
• chr17-4960115-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004890.3(SPAG7):​c.328-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,612,340 control chromosomes in the GnomAD database, including 550,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51477 hom., cov: 34)
  • Exomes 𝑓: 0.82 (499022 hom.)
• Consequence: SPAG7 NM_004890.3 splice_region, intron
• Scores: Splicing: ADA: 0.000009876
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0820
• Publications: 33 publications found

Genes affected

SPAG7 (HGNC:11216): (sperm associated antigen 7) Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SPAG7 Gene-Disease associations (from GenCC):

• PFAPA syndrome

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-4960115-A-G is Benign according to our data. Variant chr17-4960115-A-G is described in ClinVar as Benign. ClinVar VariationId is 403467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG7	NM_004890.3	MANE Select	c.328-4T>C		splice_region intron	N/A	NP_004881.2	O75391

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG7	ENST00000206020.8	TSL:1 MANE Select	c.328-4T>C		splice_region intron	N/A	ENSP00000206020.3	O75391
	SPAG7	ENST00000575142.5	TSL:1	c.295-4T>C		splice_region intron	N/A	ENSP00000461145.1	I3L4C3
	SPAG7	ENST00000859822.1		c.328-4T>C		splice_region intron	N/A	ENSP00000529881.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124377 AN: 152100 Hom.: 51415 Cov.: 34

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.853

GnomAD2 exomes AF: 0.782 AC: 195064 AN: 249480 AF XY: 0.776

Gnomad AFR exome AF: 0.837

Gnomad AMR exome AF: 0.822

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.460

Gnomad FIN exome AF: 0.788

Gnomad NFE exome AF: 0.856

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.822 AC: 1199848 AN: 1460122 Hom.: 499022 Cov.: 37 AF XY: 0.816 AC XY: 592880 AN XY: 726534

African (AFR) AF: 0.836 AC: 27960 AN: 33436

American (AMR) AF: 0.825 AC: 36883 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 22497 AN: 26116

East Asian (EAS) AF: 0.466 AC: 18516 AN: 39696

South Asian (SAS) AF: 0.599 AC: 51672 AN: 86204

European-Finnish (FIN) AF: 0.797 AC: 42571 AN: 53408

Middle Eastern (MID) AF: 0.875 AC: 5048 AN: 5766

European-Non Finnish (NFE) AF: 0.852 AC: 945975 AN: 1110432

Other (OTH) AF: 0.808 AC: 48726 AN: 60340

GnomAD4 genome AF: 0.818 AC: 124496 AN: 152218 Hom.: 51477 Cov.: 34 AF XY: 0.809 AC XY: 60259 AN XY: 74440

African (AFR) AF: 0.834 AC: 34630 AN: 41528

American (AMR) AF: 0.842 AC: 12885 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2987 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2353 AN: 5172

South Asian (SAS) AF: 0.576 AC: 2785 AN: 4832

European-Finnish (FIN) AF: 0.783 AC: 8293 AN: 10596

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57761 AN: 68002

Other (OTH) AF: 0.851 AC: 1798 AN: 2114

Alfa AF: 0.842 Hom.: 121303

Bravo AF: 0.826

Asia WGS AF: 0.560 AC: 1952 AN: 3478

EpiCase AF: 0.847

EpiControl AF: 0.858

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.63
PhyloP100		-0.082
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000099
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs238224; hg19: chr17-4863410; COSMIC: COSV52776659; COSMIC: COSV52776659;