8-7860744-A-T

Variant names:

• chr8-7860744-A-T
• rs3860876
• NM_001395484.1:c.313A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395484.1(SPAG11A):​c.313A>T​(p.Ser105Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.92 (50325 hom., cov: 19)
  • Exomes 𝑓: 0.99 (626521 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPAG11A NM_001395484.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.8364196E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

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.313A>T	p.Ser105Cys	missense	Exon 3 of 3	NP_001382413.1	A0A2R8Y853
	SPAG11A	NM_001363726.3		c.*77A>T		3_prime_UTR	Exon 4 of 4	NP_001350655.1	J3KR45
	SPAG11A	NM_001081552.3		c.292+21A>T		intron	N/A	NP_001075021.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG11A	ENST00000642566.2	MANE Select	c.313A>T	p.Ser105Cys	missense	Exon 3 of 3	ENSP00000496500.1	A0A2R8Y853
	SPAG11A	ENST00000434307.6	TSL:1	c.*77A>T		3_prime_UTR	Exon 4 of 4	ENSP00000416991.2	J3KR45
	SPAG11A	ENST00000326558.9	TSL:1	c.292+21A>T		intron	N/A	ENSP00000316012.5	A0A0A0MR37

Frequencies

GnomAD3 genomes AF: 0.921 AC: 108297 AN: 117622 Hom.: 50286 Cov.: 19

Gnomad AFR AF: 0.752

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.973

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.940

GnomAD2 exomes AF: 0.980 AC: 193179 AN: 197214 AF XY: 0.984

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.987

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.993 AC: 1259962 AN: 1269122 Hom.: 626521 Cov.: 35 AF XY: 0.994 AC XY: 624569 AN XY: 628520

African (AFR) AF: 0.765 AC: 22562 AN: 29492

American (AMR) AF: 0.984 AC: 37255 AN: 37862

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 21553 AN: 21556

East Asian (EAS) AF: 1.00 AC: 28626 AN: 28626

South Asian (SAS) AF: 1.00 AC: 65529 AN: 65556

European-Finnish (FIN) AF: 1.00 AC: 46420 AN: 46424

Middle Eastern (MID) AF: 0.992 AC: 5093 AN: 5136

European-Non Finnish (NFE) AF: 0.999 AC: 981463 AN: 982150

Other (OTH) AF: 0.984 AC: 51461 AN: 52320

GnomAD4 genome AF: 0.921 AC: 108391 AN: 117732 Hom.: 50325 Cov.: 19 AF XY: 0.922 AC XY: 51898 AN XY: 56258

African (AFR) AF: 0.752 AC: 26729 AN: 35526

American (AMR) AF: 0.969 AC: 11461 AN: 11822

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2678 AN: 2678

East Asian (EAS) AF: 1.00 AC: 2690 AN: 2690

South Asian (SAS) AF: 0.998 AC: 2779 AN: 2784

European-Finnish (FIN) AF: 1.00 AC: 7172 AN: 7172

Middle Eastern (MID) AF: 0.975 AC: 232 AN: 238

European-Non Finnish (NFE) AF: 0.999 AC: 52476 AN: 52554

Other (OTH) AF: 0.941 AC: 1502 AN: 1596

Alfa AF: 0.952 Hom.: 6410

ExAC AF: 0.975 AC: 105551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.012
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.074
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	5.8e-7	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.5
PROVEAN	Benign	8.1	N
REVEL	Benign	0.086
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.081
ClinPred		0.0062	T
GERP RS		2.3
Mutation Taster		=97/3	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3860876; hg19: chr8-7718266; COSMIC: COSV58500079;