rs774543778

Variant names:

• chr8-7848792-C-T
• rs774543778
• NM_001395484.1:c.163C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395484.1(SPAG11A):​c.163C>T​(p.Arg55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 11)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPAG11A NM_001395484.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.224
• Publications: 0 publications found

Genes affected

SPAG11A (HGNC:33342): (sperm associated antigen 11A) Involved in antimicrobial humoral immune response mediated by antimicrobial peptide and cytolysis by host of symbiont cells. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LOC124901865 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03257653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395484.1. 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
	SPAG11A	NM_001395484.1	MANE Select	c.163C>T	p.Arg55Cys	missense	Exon 2 of 3	NP_001382413.1	A0A2R8Y853
	SPAG11A	NM_001081552.3		c.163C>T	p.Arg55Cys	missense	Exon 2 of 4	NP_001075021.2
	SPAG11A	NM_001363726.3		c.163C>T	p.Arg55Cys	missense	Exon 2 of 4	NP_001350655.1	J3KR45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG11A	ENST00000642566.2	MANE Select	c.163C>T	p.Arg55Cys	missense	Exon 2 of 3	ENSP00000496500.1	A0A2R8Y853
	SPAG11A	ENST00000400125.6	TSL:1	c.163C>T	p.Arg55Cys	missense	Exon 2 of 3	ENSP00000382990.2
	SPAG11A	ENST00000326558.9	TSL:1	c.163C>T	p.Arg55Cys	missense	Exon 2 of 4	ENSP00000316012.5	A0A0A0MR37

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 108 AN: 92828 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.000166

Gnomad OTH AF: 0.00180

GnomAD2 exomes AF: 0.000228 AC: 16 AN: 70204 AF XY: 0.000142

Gnomad AFR exome AF: 0.00202

Gnomad AMR exome AF: 0.000152

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000159 AC: 118 AN: 741800 Hom.: 0 Cov.: 10 AF XY: 0.000132 AC XY: 50 AN XY: 378836

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00251 AC: 58 AN: 23138

American (AMR) AF: 0.000145 AC: 4 AN: 27630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16794

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31482

South Asian (SAS) AF: 0.0000530 AC: 3 AN: 56588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42218

Middle Eastern (MID) AF: 0.000386 AC: 1 AN: 2594

European-Non Finnish (NFE) AF: 0.0000949 AC: 48 AN: 505744

Other (OTH) AF: 0.0000842 AC: 3 AN: 35612

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00116 AC: 108 AN: 92916 Hom.: 0 Cov.: 11 AF XY: 0.000879 AC XY: 38 AN XY: 43236

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00340 AC: 95 AN: 27944

American (AMR) AF: 0.000393 AC: 3 AN: 7630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2342

East Asian (EAS) AF: 0.00 AC: 0 AN: 3094

South Asian (SAS) AF: 0.00 AC: 0 AN: 2216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5606

Middle Eastern (MID) AF: 0.00403 AC: 1 AN: 248

European-Non Finnish (NFE) AF: 0.000166 AC: 7 AN: 42152

Other (OTH) AF: 0.00178 AC: 2 AN: 1126

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000612 Hom.: 0

ExAC AF: 0.0000489 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.014	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.22
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.081
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Vest4		0.20
MVP		0.28
MPC		2.6
ClinPred		0.096	T
GERP RS		0.090
gMVP		0.063
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs774543778; hg19: chr8-7706314;