8-7860667-G-C

Variant names:

• chr8-7860667-G-C
• rs775284324
• ENST00000434307.6:c.312G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000434307.6(SPAG11A):​c.312G>C​(p.Ter104Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 134,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000074 (0 hom., cov: 26)
• Consequence: SPAG11A ENST00000434307.6 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000434307.6 Downstream stopcodon found after 158 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG11A	NM_001395484.1	c.236G>C	p.Arg79Thr	missense_variant	Exon 3 of 3	ENST00000642566.2	NP_001382413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG11A	ENST00000642566.2	c.236G>C	p.Arg79Thr	missense_variant	Exon 3 of 3		NM_001395484.1	ENSP00000496500.1

Frequencies

GnomAD3 genomes AF: 0.00000744 AC: 1 AN: 134402 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000167

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 51

GnomAD4 genome AF: 0.00000744 AC: 1 AN: 134402 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 65092

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

African (AFR) AF: 0.00 AC: 0 AN: 38934

American (AMR) AF: 0.00 AC: 0 AN: 13596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3078

East Asian (EAS) AF: 0.00 AC: 0 AN: 3462

South Asian (SAS) AF: 0.00 AC: 0 AN: 3620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000167 AC: 1 AN: 59868

Other (OTH) AF: 0.00 AC: 0 AN: 1842

⚠️ 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: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	23
DANN	Benign	0.78
DEOGEN2	Benign	0.14	.;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.75	T;.;T
MetaRNN	Benign	0.0037	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	.;D;D
Sift4G	Uncertain	0.0080	.;D;D
Vest4		0.63, 0.71
MutPred		0.62		Loss of MoRF binding (P = 0.2043);Loss of MoRF binding (P = 0.2043);.;
MVP		0.030
MPC		0.015
ClinPred		0.59	D
GERP RS		2.3
gMVP		0.076
Mutation Taster		=168/32	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs775284324; hg19: chr8-7718189;